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Aims Currently, virtual reality (VR) constitutes a vital aspect of digital health, necessitating an overview of study trends. We classified type A studies as those in which health care providers utilized VR devices and type B studies as those in which patients employed the devices. This study aimed to analyse the characteristics of each type of studies using natural language processing (NLP) methods. Methods and results Literature related to VR in cardiovascular research was searched in PubMed between 2010 and 2022. The characteristics of studies were analysed based on their classification as type A or type B. Abstracts of the studies were used as corpus for text mining. A binary logistic regression model was trained to automatically categorize the abstracts into the two study types. Classification performance was evaluated by accuracy, precision, recall, F-1 score, and c-statistics of the receiver operator curve (ROC) analysis. In total, 171 articles met the inclusion criteria, where 120 (70.2%) were type A studies and 51 (29.8%) were type B studies. Type A studies had a higher proportion of case reports than type B studies (18.3% vs. 3.9%, P = 0.01). As for abstract classification, the binary logistic regression model yielded 88% accuracy and an area under the ROC of 0.98. The words ‘training’, ‘3d’, and ‘simulation’ were the most powerful determinants of type A studies, while the words ‘patients’, ‘anxiety’, and ‘rehabilitation’ were more indicative for type B studies. Conclusions NLP methods revealed the characteristics of the two types of VR-related research in cardiology.

Background For relief of cold symptoms, methylephedrine is considered to be safer than ephedrine, particularly when used at the predetermined dose. It is often present in various over-the-counter (OTC) drugs for cold, including paediatric cough syrups. Case summary A 52-year-old man presented with worsening dyspnoea and anorexia for 2 weeks. He was a night shift worker and had been habitually taking large doses of methylephedrine-containing paediatric cough syrup for 20 years for sleep averting. On admission, his chest X-ray revealed pulmonary congestion and electrocardiogram showed sinus tachycardia with left-axis deviation. Echocardiography revealed diffuse hypokinesis with a reduced ejection fraction (EF) of 25%. The B-type natriuretic peptide level was elevated to 1092 ng/L. Even after treatment with low-dose dobutamine and furosemide in intensive care unit, right-heart catheterization demonstrated a ‘wet and cold’ profile. Coronary angiography revealed normal coronary arteries. Pathological examination by endomyocardial biopsy revealed cardiomyocyte hypertrophy with moderate interstitial and replacement fibrosis. In addition, cardiac magnetic resonance imaging revealed diffuse hypokinesis with mid-wall late gadolinium enhancement, which suggested fibrosis. Discontinuation of the cough syrup and optimal medical treatment with an angiotensin-converting enzyme inhibitor and a β blocker resulted in improvement in the heart failure symptoms to New York Class Association Class II. The EF also improved to 50% at 4 months after discharge. Discussion Methylephedrine is considered to have adrenergic effects; it has milder side effects on the cardiovascular system than ephedrine. However, the long-lasting excessive intake of methylephedrine, even through OTC paediatric cough syrups, has the potential to cause heart failure.

Objective To investigate a mechanistic determinant of left atrial (LA) reservoir function in patients presenting left ventricular (LV) hypertrophy, and clarify diagnostic and prognostic values of LA reservoir strain in patients with cardiac amyloidosis (CA). Methods Three-hundred sixty patients (median age: 68 years, male gender: 65%) with left ventricular hypertrophy (LVH) assessed by echocardiography were retrospectively included. The LVH etiologies were diagnosed by any of biopsy, cardiac magnetic resonance imaging or 99mTc-PYP scintigraphy. LV segmental longitudinal strain was estimated from apical three views, and LA reservoir strain was measured from an apical 4-chamber view. Results The LVH etiologies were confirmed with CA in 81 patients, hypertensive heart disease in 87 patients, hypertrophic cardiomyopathy in 143 patients, and miscellaneous disorders in 49 patients. The median (25th, 75th percentile) value of LV ejection fraction was 59% (48–67). LV basal longitudinal strain and LA reservoir strain were significantly reduced in patients with CA compared with those with other etiologies; LV basal strain: 5.4% (3.9–8.7) vs. 11.9% (9.3–14.6), LA reservoir strain: 9.2% (6.3–12.3) vs. 17.5% (11.3–24.1), p Conclusions The decrease of LV longitudinal shortening at cardiac base could worsen LA reservoir function especially in patients with CA. LA reservoir strain might be an alternative measure to identify CA etiology and have a predictive value of heart failure hospitalization in patients with LV hypertrophy. Funding Acknowledgement Type of funding sources: None.

Introduction Atrial fibrillation (AF) promotes left atrial (LA) remodeling and vice versa. LA volume index (LAVI) ≥34 mL/m2 is an established cut-off value for identifying an enlarged left atrium. Catheter ablation has become an established therapy for AF and provides a reduction of LA volume by maintaining sinus rhythm (reverse remodeling). However, the definition of LA reverse remodeling after AF ablation is undetermined. Purpose We hypothesized that patients with LA dilatation who obtain normal LA volume (LAVI Methods We enrolled 140 AF patients with baseline LAVI ≥34 mL/m2, without AF recurrence for 1 year after the initial AF ablation. We acquired conventional and speckle-tracking echocardiographic parameters within 24 h and at 1 year after the procedure. Late recurrence was defined as AF recurrence >1 year after the initial ablation. To define the normal range of LA function, age-and sex-matched 140 controls without a history of AF were also enrolled. Results After restoration of sinus rhythm, overall LA structural and functional parameters were significantly improved, and 75 patients (54%) had normal LA volume at the time of follow-up (Table). During a median follow-up of 44 (31–61) months, 32 patients (23%) experienced a late recurrence of AF. Patients who obtained normal LA volume after AF ablation had fewer late recurrences than those who did not (P Conclusion Patients who obtain normal LA volume have better long-term outcomes of AF ablation than those who do not. Although AF ablation promotes beneficial effects on LA structure and function, LA function cannot be normalized even in patients who obtain normal LA volume after successful ablation. Thus, physicians should carefully consider long-term follow-up and residual AF risks, regardless of sinus rhythm restoration by catheter ablation. Funding Acknowledgement Type of funding sources: None.

Background Cardiac amyloidosis (CA), characterized by amyloid protein deposition in the heart, is a treatable disease. Although left ventricular (LV) wall thickness is the most established imaging predictor for CA, several echocardiographic indices including deformation parameters also contribute to the screening of CA. However, it is unclear whether additive values of echocardiographic indices have greater benefit over the conventional clinical predictors for the screening of CA. Therefore, we sought to compare the incremental benefits of echocardiographic indices over the clinical parameters for the screening of CA and externally validate their incremental benefits. Methods We retrospectively studied 295 consecutive patients (median age, 67 years; male, 65%; mean LV wall thickness (MWT), 12 mm) with LV hypertrophy who underwent echocardiography as well as the detailed work-up for myocardium (Biopsy, technetium pyrophosphate scintigraphy (99mTc-PYP) or cardiac magnetic resonance imaging). CA was diagnosed through biopsy or 99mTc-PYP. The clinical model considers patients' age and the low-voltage in electrocardiography in reference to previous studies. Continuous echocardiographic variables were represented in binary through generally accepted external cutoff points. The incremental benefits of the echocardiography findings over the clinical model were assessed using with the help of both receiver-operated characteristic curve analysis and comparison of area under the curves. Furthermore, these incremental benefits were validated in the external validation sample (median age, 70 years; male, 69%; MWT, 12 mm). Results Among the enrolled patients, CA was observed in 18% of cases. Table presents the results of this study. Of the echocardiographic parameters, relative apical sparing pattern (RASP) was the greatest contributor for improvement of diagnostic accuracy of the clinical model. The next greatest contributor was LV wall thickness, followed by left atrial reservoir strain (LAS), E/e', left atrial volume index, ejection fraction strain ratio, and pericardial effusion, respectively. Similarly, RASP, LV wall thickness, global longitudinal strain, ejection fraction, LAS, and granular sparkling showed significant incremental benefit in the validation cohort. Only mean wall thickness, LV wall thickness, LAS, E/e' and RASP consistently improved the diagnostic accuracy of the clinical model. Conclusion During the screening process, adding LV wall thickness, LAS, and RASP to the clinical parameters may be useful for the accurate diagnosis of CA in patients with LV hypertrophy. Figure 1 Funding Acknowledgement Type of funding source: None

Background The peak oxygen uptake (VO2) evaluated by the cardiopulmonary exercise test (CPX) is an established marker of exercise capacity in patients with heart failure (HF). In particular, peak VO2 Purpose We evaluated whether RV dysfunction assessed by the low-load ESE determined a low peak VO2 Methods We studied 67 consecutive hospitalized patients with HF (mean age, 65 years; 75% male; mean LV ejection fraction, 36%) who underwent ESE and CPX after stabilized HF condition, and the time interval of CPX and ESE tests was within 48 hours. CPX was performed using an upright cycle ergometer by a ramp protocol, while ESE was performed using ergometer in semi-supine position and the workload was generally increased by 25 watts every 3 minutes. The low-load ESE was defined as the 25 watts exercise. The increments of RV s' velocity at tricuspid annulus and RV strain in the free wall were considered as a preservation of RV contractile reserve. Among the study population, 26 patients were performed right heart catheterization and RV dP/dt/Pmax was estimated as an invasive marker of RV contractility. Results The achieved intensity of exercise was 50.4±21.0 watts, and all patients completed the low-load ESE. The invasive study showed that the change of RV s' velocity during the low-load ESE significantly correlated with RV dP/dt/Pmax (r=0.706, p Conclusion The change of RV s' velocity during the low-load ESE could determine exercise tolerance in patients with HF. The assessment of RV contractile reserve might be clinically useful to discriminate high risk HF patients. Figure 1 Funding Acknowledgement Type of funding source: None

Background Cardiac amyloidosis (CA) is an infiltrative disease mimicking left ventricular hypertrophy (LVH), although its prognosis is poorer than other diseases with LVH. Moreover, because CA is treatable, appropriate screening for CA is an important area of study for clinicians to prevent and treat the disease. Several imaging predictors of CA have been reported so far;. in particular, deformation parameters such as relative apical sparing patterns of longitudinal strain (RASP) may diagnose CA with better precision than conventional parameters. Accordingly, we hypothesized that the inclusion of deformation parameters into the established diagnostic parameters would permit derivation of a risk score for CA screening in patients with LVH. Thus, we aimed to 1) investigate the incremental benefits of deformation parameters over established diagnostic parameters for CA screening in patients with LVH; 2) determine the risk score to screen CA patients with LVH using all of these variables; and 3) externally validate the score. Methods We retrospectively studied 295 consecutive non-ischemic patients with LVH who underwent echocardiography as well as the detailed work-up for LVH (biopsy, technetium pyrophosphate scintigraphy (99mTc-PYP) or cardiac magnetic resonance imaging) (median age, 67 years; MWT, 12 mm). CA was diagnosed by biopsy or 99mTc-PYP. The base model consisted of age (≥65 [male], ≥70 [female]), low voltage in electrocardiography, and posterior wall thickness ≥14 mm in reference to previous studies. Continuous echocardiographic variables were binarized by the use of generally accepted external cutoff points to avoid best clinical scenario. Incremental benefits were assessed using receiver operating characteristic curve analysis and area under the curve (AUC) comparison. Multiple logistic regression analysis was performed to determine the risk score. The score was then validated in the external validation sample (N=178, median age, 70 years; MWT, 12 mm). Results CA was observed in 54 patients (18%) and of the several echocardiographic parameters studied, only RASP demonstrated a significant incremental benefit for the screening of CA over the base model (Figure A). After multiple logistic regression analysis in the prediction of CA with 4 variables (RASP and basal model components), each was assigned a numeric value based on its relative effect (Figure B). The incidence rate of CA clearly increased as the sum of the risk score increased (Figure C). The score had good discrimination ability, with an AUC of 0.87, a total score of ≥2 with 70% sensitivity and 90% specificity. Similarly, the discrimination ability of the score in the validation cohort was sufficient (AUC = 0.87). Conclusion Overall, we determined a simple risk score including RASP to screen CA. This score takes into account 4 common parameters used in daily practice, and therefore, has potential utility in risk stratification and management of patients with LVH. Figure 1 Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): Kitaishikai

Background The relative apical sparing pattern (RASP) of left ventricular (LV) longitudinal strain (LS) is frequently associated with cardiac amyloidosis (CA). However, some patients with CA do not show the RASP, and their clinical characteristics have not been fully clarified. We sought to investigate the clinical significance of RASP in patients with CA. Methods One hundred consecutive CA patients who were diagnosed by biopsy or myocardial pyrophosphate scintigraphy and evaluated for RASP (mean age: 76 years, male: 77%, LV mean wall thickness: 13.5 mm, light-chain [AL] type: 33 cases, transthyretin [TTR] type: 67 cases) were retrospectively enrolled. The RASP was semi-quantitatively and quantitatively assessed. Semi-quantitative RASP was defined as reduction of LS (≥−10%) in ≥5 (of 6) basal segments relative to preserved LS (1.00, >0.90, and >0.87) according to the literature. Results Semi-quantitative and binalized quantitative RASP (>1.00, >0.90, and >0.87) were observed in 55, 55, 63, and 65 patients, respectively. RASP in each definition was more prevalent in the TTR group than in the AL group. Additionally, RASP was significantly associated with higher LV wall thickness even after adjustment for the CA subtypes (all, p Conclusions The incidence of RASP is low in the case of thin LV wall thickness in CA patients, which may indicate the difficulty of early diagnosis of CA using RASP in patients with mild LV hypertrophy. The prognostic prediction using RASP may be challenging in this cohort. Figure 1 Funding Acknowledgement Type of funding source: None

Background Quantitative myocardial perfusion imaging with CT is increasingly used for the diagnosis of coronary artery disease. Relative flow reserve (RFRCT) derived from dynamic stress CT perfusion (CTP) is defined as the ratio between myocardial blood flow (MBF) in the stenosis-related territory and MBF in the non-stenosis-related territory. Purpose We sought to evaluate whether RFRCTcan be used as a non-invasive method for detection of functionally significant coronary artery stenosis compared with stress MBF. Methods This study was retrospectively included 31 consecutive patients (40 vessels) with coronary artery disease and examined with CT angiography, CTP, coronary angiography, and FFR. RFRCT and stress MBF results were compared with invasive FFR using a threshold of 0.80. Results The RFRCT values were significantly correlated to FFR values (R2=0.788, P Figures 1 & 2 Conclusions RFRCT was superior to stress MBF for detecting abnormal FFR in patients with stable coronary artery disease.

Background Left atrial (LA) involvement of abnormal amyloid fibrils could induce LA dysfunction and stiffening in patients with cardiac amyloidosis (CA). Thus, the assessments of LA function and stiffness might be a potential approach to diagnose CA phenotype among patients with hypertrophied hearts. Purpose We sought to determine whether LA reservoir strain with speckle tracking echocardiography could be used a marker of LA stiffness in a derivation cohort. Furthermore, we tested to our hypothesis that LA reservoir strain could differentiate CA patients from hypertrophic cardiomyopathy (HCM) in an independent validation cohort. Methods In the derivation cohort, echocardiography was performed simultaneously with measurements of pulmonary capillary wedge pressure (PCWP) in 50 patients with suspected or established heart failure and relatively preserved left ventricular (LV) ejection fraction (56±10%). LA maximum and minimum volume index, and reservoir strain were measured from apical four-chamber view. LA stiffness index was computed as a pressure rise from x-trough to v-wave divided by an increase from minimum to maximum indexed LA volume (Figure A). In an independent validation group, we studied a total of 33 biopsy-proved CA patients and 127 HCM patients (LV ejection fraction: 57±11% vs. 66±10%, P Results The derivation cohort study found that there was a significant curvilinear correlation of LA reservoir strain to LA stiffness index (Figure B). In the validation cohort, LA reservoir strain was reduced in patients with CA compared with HCM in all participants (11.6±5.6% vs. 18.5±6.9%, P Conclusions LA reservoir function was fairly limited in patients with CA compared with HCM. Restricted LA motion might be related to atrial amyloid deposits or fibrosis, which potentially provokes atrial chamber stiffening.

Background/Introduction Long-term efficacy following catheter ablation (CA) of atrial fibrillation (AF) remains unknown. Left atrial (LA) reverse remodeling following CA may be important to reduce the risk of very late recurrence (VLR). Purpose We hypothesize that improved mechanical conduction delay with myocardial strain is associated with LA reverse remodeling indicates efficacy following AF ablation. This study aimed to investigate the clinical utility of mechanical conduction delay to predict VLR in patients with AF undergoing CA. Methods We enrolled 114 consecutive patients undergoing initial CA in patients with AF from January 2012 to February 2014. 20 patients were excluded due to poor echocardiographic image quality. 38 patients had AF recurrence within 12 months after CA. Finally, 54 patients (age 62 years, 13 female, 15 persistent AF) were analyzed. Trans-thoracic echocardiography (TTE) was performed within 24 hours as baseline, and every 6–12 months following the initial CA as follow-up. We compared the TTE data with baseline and latest test when sinus rhythm was maintained. To assess atrial electromechanical conduction delay, we adopted a parameter based on speckle tracking echocardiography (EMT-ε), which was defined as the interval from the P- wave onset to the peak late diastolic longitudinal strain in the basal lateral wall of LA (Figure). Results Eleven patients had VLR after CA. In patients with VLR, left atrial volume index (LAVI) at baseline was significantly higher than those without VLR (49±17 vs 35±14 ml/m2, P During 58±22 months, LAVI and EMT-ε were significantly improved (LAVI: 38±16 vs 33±14 ml/m2, EMT-ε: 215±48 vs 197±45 ms, P Conclusion(s) The atrial electromechanical conduction delay could predict VLR after CA in patients with AF.

The present study showed that treatment with a cell membrane-impermeable metal ion chelator, EDTA, of porcine oocytes at the germinal vesicle (GV) stage collected from follicles 2‐6 mm in diameter induced artificial activation followed by formation of a pronucleus (PN). When the oocytes were cultured for 48 h in medium containing 0.1 to 2 mM EDTA disodium salt (Na-EDTA), they were activated to form PN, and the maximum PN formation rate (63%, n 5 68) was achieved in oocytes cultured with 1 mM Na-EDTA. More than 90% of oocytes activated by 1 mM Na-EDTA treatment formed 1 PN without emission of the first and the second polar bodies (PB). This result suggests that EDTA at 1 mM may force the maturing (meiosis I) oocytes to form a PN without chromosome segregation. When oocytes at the GV stage that had been cultured with 1 mM Na-EDTA for 48 h were further cultured in 0.4% BSA-containing NCSU23 medium for 144 h, blastocysts that appeared to be morphologically normal were formed at the rate of 10%, whereas no blastocysts were formed from oocytes that had not been cultured with Na-EDTA. Next we examined the effects of Ca 21 ,Z n 21 ,F e 31 ,o r Cu 21 -saturated EDTA (Ca-EDTA, Zn-EDTA, Fe-EDTA, and Cu-EDTA, respectively), and a Ca 21 -specific chelator, EGTA, at a concentration of 1 mM. The Ca-EDTA, FeEDTA, and Cu-EDTA, but not Zn-EDTA or EGTA, had the ability to activate the oocytes. From these results, it is suggested that extracellular chelation of Zn 21 with EDTA of maturing (meiosis I) porcine oocytes results in parthenogenetic activation of the oocytes, which induces PN formation followed by development to blastocysts. developmental biology, implantation/early development, oocyte development

Midkine (MK) is known to be a member of a new family of heparin-binding growth/differentiation factors, together with pleiotrophin, and to be quite rich in bovine follicular fluid. To examine whether treatment with MK during in vitro maturation (IVM) of bovine granulosa-enclosed oocytes affects their nuclear maturation and postfertilization development to the blastocyst stage, bovine granulosa-enclosed oocytes obtained from slaughterhouse-derived ovaries were cultured for 24 h in IVM medium without (control) or with various concentrations (1-500 ng/ml) of MK, followed by in vitro fertilization (IVF) and culturing. Although the MK treatment during IVM did not affect the rate of nuclear maturation or the postfertilization cleavage of oocytes, MK at > or = 10 ng/ml significantly (P: < 0.05) increased the blastocyst yields per tested and per cleaved oocyte compared with the case of the control. Next, the effects of various glycosaminoglycans (heparin, heparan sulfate, chondroitin sulfate A and C, and hyaluronic acid) preincubated with MK at 50 ng/ml were examined. The enhancing activity of MK was completely suppressed by heparin at 600 ng/ml but not by the other compounds. The effects of MK during IVM were also tested on oocytes freed from granulosa cells (GCs). When the denuded oocytes were cultured in IVM medium, no blastocyst formation after IVF was observed, regardless of MK supplementation. However, coculture of the denuded oocytes with isolated GC pellets enhanced the cleavage rates and the blastocyst yield, and these effects were more pronounced with MK supplementation. These results indicate that the presence of MK during IVM of bovine granulosa-enclosed oocytes can enhance their developmental competence to the blastocyst stage after IVF and suggest that the enhancing effects might be mainly mediated by GCs.

This study was designed to assess heart performance in young (10-week-old) spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, in terms of whole heart function in vivo and mechanics of isolated ventricular myocytes in vitro. The data suggest that left ventricular pressure (LVP) generation is greater, and the maximal velocities of LVP generation and decline are faster in SHR than in WKY. Two-dimensional morphologic measurements show that SHR myocytes are hypertrophied and that augmented contractile function is also present in isolated cells as determined by the extent of shortening and velocity of shortening. Relaxation is also faster at the myocyte level as determined by velocity of relengthening. However, the slope of the relationship between myocyte peak shortening and velocity of relaxation was similar in both groups. These results suggest that hyperdynamic myocyte relengthening may reflect changes in elastic recoil from increased shortening rather than intrinsic changes in cellular mechanisms, which are independent of shortening.