Mitral Valve Early Systolic Billowing Induces Following Annular Expansion and Leaflet Augmentation in Barlow's Disease: Sequential Analysis using Three-dimensional Echocardiography.

AIMS: Although systolic expansion of the annulus has been recognized in Barlow's disease, the mechanisms of the unique pathological movement of the annulus and its relation to the leaflet augmentation has not yet been clarified. We aimed to investigate the detailed mechanisms of the characteristic mitral apparatus dynamics in Barlow's disease by frame-by-frame sequential geometric analysis using real-time three-dimensional transesophageal echocardiography. METHODS AND RESULTS: Fifty-three patients with Barlow's disease and severe mitral regurgitation without torn chordae, as well as 10 controls, were included. We evaluated geometric changes in the mitral complex using three-dimensional transesophageal echocardiography at five points during systole. To identify early systolic billowing of leaflets, the annulo-leaflet angle was measured. We also performed a more detailed analysis in four consecutive frames just before and after leaflet free-edge prolapse above the annulus plane. The median annulo-leaflet angle of both leaflets in early systole was greater than 0° (above annulus plane) in patients with Barlow's disease, and billowing of the leaflet body were observed from early systole. The prolapse volume of both leaflets increased markedly from early to mid-systole (1.60 [0.85-2.80] to 4.00 [2.10-6.45] mL; analysis of variance, p < 0.001; post-hoc, p < 0.05). With frame-by-frame analysis, dynamic augmentation of the annulus and leaflets developed between frames just before and just after leaflet free-edge prolapse (analysis of variance, p < 0.01; post-hoc, p < 0.05). CONCLUSIONS: In Barlow's disease, early systolic billowing of the mitral leaflet induces systolic annulus expansion followed by leaflet augmentation and leaflet free-edge prolapse.

The regenerative treatment of costal osteochondral graft implantation for partial growth arrest using a rabbit model.

PURPOSE: To investigate the feasibility of cylindrical costal osteochondral graft transplantation as a novel regenerative treatment in growth arrest. METHODS: The medial portion of the proximal tibial growth plate of 6-week-old male New Zealand White rabbits was resected to establish an experimental model of partial growth plate injury. The rabbits were divided into four groups: no-treatment, bone wax transplantation, costal chondral graft, and costal osteochondral graft groups. Radiographic and micro-computed tomography scan results were analyzed to evaluate angular deformity of the tibia and bony bridge formation at the injury site. In addition, repair of the injured growth plate cartilage was assessed histologically at 4, 8, and 12 weeks postoperatively. RESULTS: Radiographic examination revealed that bone wax transplantation continuously decreased the medial proximal tibial angle (MPTA) while the costal chondral graft implantation reduced the decrease of MPTA at 12 weeks postoperatively. The costal osteochondral graft implantation recovered the MPTA, close to the normal. Histologically, the costal osteochondral grafts retained the MPTA in the injured site compared to costal chondral grafts. Additionally, hypertrophic chondrocytes were observed at the graft site in the costal osteochondral graft group at 12 weeks, suggesting that endochondral ossification may occur at the graft site similar to normal ossification. The fluorescence in situ hybridization analysis of osteochondral grafts transplanted from male to female rabbits indicated that they were replaced by cells of host origin. CONCLUSION: The costal osteochondral graft can achieve regeneration without bony bridge formation in partial growth plate injury.

Dynamic changes in echocardiographic parameters in acute decompensated heart failure: REALITY-ECHO.

BACKGROUND: Appropriate evaluation of hemodynamic status is vital in the management of acute heart failure (AHF). We aimed to investigate the changes in echocardiographic parameters during very acute phases of AHF and their association with clinical outcomes. METHODS: Patients who were admitted to four Japanese hospitals with AHF were prospectively enrolled. Comprehensive echocardiography and B-type natriuretic peptide (BNP) were assessed both on admission and the second day. RESULTS: A total of 271 patients (80 ±â€¯12 years old, 52 % male) was included. Overall, transmitral E velocity, E/A, tricuspid regurgitation pressure gradient (TRPG), and inferior vena cava diameter significantly decreased, and stroke volume and left ventricular ejection fraction showed a significant increase by the second day, whereas E/e' did not change. On the second day, BNP increased in 50 patients (18 %). Despite similar baseline characteristics, patients with increased BNP showed a significantly smaller improvement in transmitral flow parameters (E and A velocity, E/A, and flow patterns) and a smaller decrease in TRPG compared with patients with decreased BNP. Other echocardiographic parameter changes were not different between the groups. A combination of improvement in transmitral flow and TRPG was significantly associated with 90-day and 1-year composite events of all-cause death and heart failure hospitalization after adjustment by the Get With the Guidelines-Heart Failure risk score. CONCLUSIONS: Echocardiographic parameters show a dynamic change in the very acute phase of AHF. Several parameters, such as the transmitral flow and TRPG might be useful in monitoring favorable hemodynamic change.

Development of new colloid osmotic pressure measurement method using ultrafiltration membrane during cardiopulmonary bypass.

BACKGROUND: Clinical practice of measuring colloid osmotic pressure (COP) was abandoned after correcting hypoosmolarity did not improve overall patient outcomes. However, the use of albumin and colloidal solutions has contributed to maintaining intraoperative and postoperative fluid balance at lower levels. Reduced perioperative fluid balance is consistently reported to have positive effects on clinical outcomes. Priming solutions for cardiopulmonary bypass typically include colloids; however, the optimal type of priming solution has not yet been determined. Stricter COP management may further improve postoperative courses. To achieve this, the widespread adoption of a measurement method suitable for COP monitoring during cardiopulmonary bypass is required. METHODS: A test circuit was made which measured COP using an ultrafiltration membrane method based on the changes in hydrostatic pressure that occurs across a semipermeable membrane. We then compared the measurements obtained using this method with colloidal osmometer measurements. RESULTS: COP measurements were obtained for a total of 100 tests (10 times each for 10 test solutions). The evaluation parameters included simultaneous reproducibility, correlation with the colloid osmometer, and measurement time. The results demonstrated high accuracy of the ultrafiltration membrane method, simultaneous reproducibility within 3%, a high positive correlation with the colloid osmometer (correlation coefficient: R2 = 0.99; p < 0.01), and equal time required for measurement. CONCLUSION: Measuring COP using ultrafiltration membranes solves problems within existing measurement methods. Although further improvements in the method are necessary, it has implications for future research and clinical applications.

Development of postoperative delirium prediction models in patients undergoing cardiovascular surgery using machine learning algorithms.

Associations between delirium and postoperative adverse events in cardiovascular surgery have been reported and the preoperative identification of high-risk patients of delirium is needed to implement focused interventions. We aimed to develop and validate machine learning models to predict post-cardiovascular surgery delirium. Patients aged ≥ 40 years who underwent cardiovascular surgery at a single hospital were prospectively enrolled. Preoperative and intraoperative factors were assessed. Each patient was evaluated for postoperative delirium 7 days after surgery. We developed machine learning models using the Bernoulli naive Bayes, Support vector machine, Random forest, Extra-trees, and XGBoost algorithms. Stratified fivefold cross-validation was performed for each developed model. Of the 87 patients, 24 (27.6%) developed postoperative delirium. Age, use of psychotropic drugs, cognitive function (Mini-Cog < 4), index of activities of daily living (Barthel Index < 100), history of stroke or cerebral hemorrhage, and eGFR (estimated glomerular filtration rate) < 60 were selected to develop delirium prediction models. The Extra-trees model had the best area under the receiver operating characteristic curve (0.76 [standard deviation 0.11]; sensitivity: 0.63; specificity: 0.78). XGBoost showed the highest sensitivity (AUROC, 0.75 [0.07]; sensitivity: 0.67; specificity: 0.79). Machine learning algorithms could predict post-cardiovascular delirium using preoperative data.Trial registration: UMIN-CTR (ID; UMIN000049390).

Association of Left Atrial Size With Stroke or Systemic Embolism in Patients With Atrial Fibrillation Having Undergone Bioprosthetic Valve Replacement From the BPV-AF Registry.

Background: The left atrial volume index (LAVI) is important for predicting thromboembolism in patients with non-valvular atrial fibrillation (AF), but the utility of LAVI for predicting thromboembolism in patients with both bioprosthetic valve replacement and AF remains unclear. Methods and Results: Of 894 patients from a previous multicenter prospective observational registry (BPV-AF Registry), 533 whose LAVI data had been obtained by transthoracic echocardiography were included in this subanalysis. Patients were divided into tertiles (T1-T3) according to LAVI as follows: T1 (n=177), LAVI=21.5-55.3 mL/m2; T2 (n=178), LAVI=55.6-82.1 mL/m2; T3 (n=178), LAVI=82.5-408.0 mL/m2. The primary outcome was defined as either stroke or systemic embolism for a mean (±SD) follow-up period of 15.3±4.2 months. Kaplan-Meier curves indicated that the primary outcome tended to occur more frequently in the group with the larger LAVI (log-rank P=0.098). Comparison of T1 with T2 plus T3 using Kaplan-Meier curves indicated that patients in T1 experienced significantly fewer primary outcomes (log-rank P=0.028). Furthermore, univariate Cox proportional hazard regression showed that 1.3- and 3.3-fold more primary outcomes occurred in T2 and T3, respectively, than in T1. Conclusions: Larger LAVI was associated with stroke or systemic embolism in patients who had undergone bioprosthetic valve replacement and with a definitive diagnosis of AF.

Comparison of Direct Oral Anticoagulants and Warfarin in Patients With Atrial Fibrillation and an Aortic Bioprosthetic Valve.

BACKGROUND: Current guidelines equally recommend direct oral anticoagulants (DOACs) and warfarin for atrial fibrillation (AF) patients with a bioprosthetic valve (BPV); however, there are limited data comparing DOACs and warfarin in AF patients with an aortic BPV.Methods and Results: This post-hoc subgroup analysis of a multicenter, prospective, observational registry (BPV-AF Registry) aimed to compare DOACs and warfarin in AF patients with an aortic BPV. The primary outcome was a composite of stroke, systemic embolism, major bleeding, heart failure requiring hospitalization, all-cause death, or BPV reoperation. The analysis included 479 patients (warfarin group, n=258; DOAC group, n=221). Surgical aortic valve replacement was performed in 74.4% and 36.7% of patients in the warfarin and DOAC groups, respectively. During a mean follow up of 15.5 months, the primary outcome occurred in 45 (17.4%) and 32 (14.5%) patients in the warfarin and DOAC groups, respectively. No significant difference was found in the primary outcome between the 2 groups (adjusted hazard ratio: 0.88, 95% confidence interval: 0.51-1.50). No significant multiplicative interaction was observed between the anticoagulant effects and type of aortic valve procedure (P=0.577). CONCLUSIONS: Among AF patients with an aortic BPV, no significant difference was observed in the composite outcome of adverse clinical events between patients treated with warfarin and those treated with DOACs, suggesting that DOACs can be used as alternatives to warfarin in these patients.

Antithrombotic Therapy for Patients With Atrial Fibrillation and Bioprosthetic Valves　- Real-World Data From the Multicenter, Prospective, Observational BPV-AF Registry.

BACKGROUND: Although bioprosthetic valve (BPV) replacements are becoming more common within our aging society, there are limited prospective data on the appropriate antithrombotic therapy for East Asian patients with atrial fibrillation (AF) and BPV replacement. Antithrombotic therapy and thrombotic and hemorrhagic event rates in Japanese patients with AF and BPV replacement are investigated.Methods and Results:This multicenter, prospective, observational study enrolled patients with BPV replacement and AF. The primary efficacy outcome was stroke or systemic embolism, and the primary safety outcome was major bleeding. Of the 894 patients analyzed, 54.7%, 29.4%, and 9.6%, were treated with warfarin-based therapy, direct oral anticoagulant (DOAC)-based therapy, or antiplatelet therapy without anticoagulants, respectively; 6.3% did not receive any antithrombotic drugs. The mean observation period was 15.3±4.0 months. The event rates for stroke or systemic embolism and major bleeding were 1.95%/year and 1.86%/year, respectively. The multivariate adjusted hazard ratios for DOAC vs. warfarin were 1.02 (95% confidence intervals [CI], 0.30-3.41 [P=0.979]) for systemic embolic events and 0.96 (95% CI, 0.29-3.16 [P=0.945]) for major bleeding. CONCLUSIONS: Approximately 30% of patients with AF and BPV replacement were treated with DOAC. The risks of major bleeding and stroke or systemic embolism were similar between warfarin- and DOAC-treated patients with AF who had BPV replacement. Treatment with DOACs could be an alternative to warfarin in this population.

Clinical Impact of Flow Adjusted Transmitral Pressure Gradient After Surgical Annuloplasty for Functional Mitral Regurgitation.

Downsizing of mitral annulus due to mitral annuloplasty for ischemic functional mitral regurgitation (FMR) raises a new issue, functional mitral stenosis (FMS), defined as a decline of mitral hemodynamics. However, common mitral hemodynamic parameters are influenced by transmitral flow, therefore, the clinical impacts are still controversial. The aim of this study is to seek mitral hemodynamic indices (including transmitlra pressure gradient [TMPG] adjusted by left ventricular stroke volume [LVSV]) relevant to the mid-term outcomes after annuloplasty for ischemic functional mitral regurgitation (FMR). This study is a retrospective evaluation of mitral valve hemodynamic status by resting echocardiogram at several weeks after surgery. Eighty-one patients underwent mitral annuloplasty for ischemic FMR between September 2012 and June 2019. Postoperative adverse events occurred in 28 patients (34.6%), and the overall 5-year freedom from adverse events rate was 55.9%. Common mitral hemodynamic parameters were not associated with adverse events, but flow adjusted TMPG can be a correlative factor. By multivariable analysis, postoperative systolic pulmonary artery pressure and peak TMPG/LVSV were detected as independent predictors (adjusted hazard ratio 1.07 and 1.08, P < 0.001 and < 0.001). Additionally, risk stratification by peak TMPG (cut-off: 10 mm Hg) and LVSV (cut-off: 35 mL/m2) reflected the mid-term outcomes, perceptively (P = 0.007). Conventional mitral hemodynamic parameters were not associated with adverse cardiac events after annuloplasty for ischemic FMR. However, flow adjusted TMPG was identfied as an independent predictor, and risk stratification by peak TMPG and LVSV reflected the mid-term outcomes, perceptively.

Physiological and prognostic differences between types of exercise stress echocardiography for functional mitral regurgitation.

OBJECTIVE: Secondary mitral regurgitation (MR) demonstrates dynamic change during exercise. This prospective observational study aimed to compare exercise stress echocardiography (ESE) where handgrip exercise (handgrip-ESE) or semisupine ergometer exercise was performed (ergometer-ESE) for patients with secondary MR. METHODS: Handgrip-ESE and symptom-limited ergometer-ESE were performed for 53 patients (median age (IQR): 68 (58-78) years; 70% male) on the same day. Baseline global longitudinal strain (GLS) was 9.2% (6.0%-14.0%) and MR volume was 20 (14-26) mL. All-cause death and cardiac hospitalisation were tracked for median 439 (101-507) days. RESULTS: Handgrip-ESE induced slightly but significantly greater degrees of MR increase (median one grade increase; p<0.001) than ergometer-ESE, although the changes in other parameters, including GLS (+1.1% vs -0.6%, p<0.001), were significantly smaller. Correlations between the two examinations with respect to the changes in the echocardiographic parameters were weak. Kaplan-Meier analyses revealed poor improvement in GLS during ergometer-ESE, but not the change in MR, was associated with adverse events (p=0.0065). No echocardiographic change observed during handgrip-ESE was prognostic. After adjusting for a clinical risk score, GLS changes during ergometer-ESE remained significant in predicting the adverse events (HR 0.39, p=0.03) A subgroup analysis in patients with moderate or greater MR at baseline (n=27) showed the same results as in the entire cohort. CONCLUSIONS: The physiological and prognostic implications of handgrip-ESE and ergometer-ESE findings significantly differ in patients with left ventricular dysfunction and secondary MR. The type of exercise to be performed in ESE should be carefully selected.

Relations of Augmented Systolic Annular Expansion and Leaflet/Papillary Muscle Dynamics in Late-Systolic Mitral Valve Prolapse Evaluated by Echocardiography with a Speckle Tracking Analysis.

The mechanism of systolic annular expansion in mitral valve prolapse (MVP) is not clarified. Since annular expansion is systolic outward shift of MV leaflet/chorda tissue complex at superior and outer ends, annular expansion could be related to inward (superior) shift of the complex at another inferior and inner end of the papillary muscle (PM) tip and/or systolic lengthening of the tissue complex, especially MV leaflets.MV annulus systolic expansion, PMs' systolic superior shift, and MV leaflets' systolic lengthening were evaluated by echocardiography with a speckle tracking analysis in 25 normal subjects, 25 subjects with holo-systolic MVP and 20 subjects with late-systolic MVP.PMs' superior shift, MV leaflets' lengthening, MV annular area at the onset of systole and subsequent MV annulus expansion were significantly greater in late-systolic MVP than in holo-systolic MVP (4.6 ± 1.6 versus 1.5 ± 0.7 mm/m2, 2.5 ± 1.4 versus 0.6 ± 2.0 mm/m2, 6.8 ± 2.5 versus 5.7 ± 1.0 cm2/m2 and 1.6 ± 0.8 versus 0.1 ± 0.5 cm2/m2, P < 0.001, respectively). Multivariate analysis identified MV leaflets' lengthening and PMs' superior shift as independent factors associated with MV annular expansion.Conclusions: These results suggest that systolic MV annular expansion in MVP is related to abnormal MV leaflets' lengthening and PMs' superior shift.