Resolving late failure of dental implant is difficult and costly; however, only few reviews have addressed the risk factors associated with late failure of dental implant. The aim of this literature review was to summarize the influences of different potential risk factors on the incidence of late dental implant failure. The protocol of this systematic review was prepared and implemented based on the PRISMA  guideline. In December 2018, studies published within the previous 10 years on late dental implant failure were selected by fulfilling the eligibility criteria and the risk factors identified in qualified studies were extracted by using a predefined extraction template. Fourteen eligible studies were assessed. The common risk factors for late failure were divided into three groups according to whether they were related to (1) the patient history , (2) clinical parameters (posterior implant location and bone grade 4) or (3) decisions made by the clinician . Clinicians should be cautions throughout the treatment process of dental implant—from the initial examination to the treatment planning, surgical operation and prosthesis selection—in order to minimize the risk of late failure of dental implant. Dental implants have become a common choice among the treatment options for missing teeth rehabilitation since they were first introduced by Branemark in the 1970s ,3. TheseEarly failure represents a failure to establish osseointegration of dental implants, while late failure is the failure of either the established osseointegration or function of dental implants . While eThe interval from a diagnosis of dental implant failure to its removal is significantly longer in late failure than early failure, and late failure is also associated with greater bone loss . MoreovePrevious studies have indicated that peri-implantitis and implant overloading were common risk factors for late failure ,10, but The protocol of this systematic review was prepared and implemented based on the PRISMA guideline . The purThe following criteria were applied to identify eligible articles for inclusion in this review: (1) involving human subjects and (2) the article published within 10 years of the search date. Articles were excluded due to any of the following reasons: (1) reporting on an in vitro study or being a case report, letter to the editor or review; (2) no definitive conclusion reported regarding the late dental implant failure; or (3) placement of implants other than of the dentoalveolar type, such as zygomatic or subperiosteal implants.An electronic search was performed on 1 December 2018 of the PubMed database to retrieve articles published in English during the previous 10 years. The following search string was used for retrieving potential articles: “dental implan* [Mesh] AND late [all fields] AND failur* [all fields]”. This search strategy was applied with the aim of identifying as many relevant publications as possible.The searched articles were independently assessed by two reviewers. All of the identified articles’ title were screened to determine the number of Abstracts to be examined. In the next round, article Abstracts were screened for whether the study contents potentially matched the purpose of this review. A consensus was achieved between the reviewers on the qualified list of articles for the next round of the review. The full texts of all eligible articles were then read, and articles that did not fulfill the eligibility criteria were eliminated. The references lists of the articles were manually searched to analyze further relevant studies. A consensus was also achieved at the end of this round between the two reviewers on the final list of articles for further data extraction. Cohen’s kappa was used to estimate the interexaminer reliability.A Microsoft Excel worksheet was used to collect data extracted from the eligible articles. The following information was extracted: name of the first author, year of publication, study design, number of patients, number of implants placed, number of patients with late-failure implants, number of late-failure implants, follow-up duration and risk factors for late-failure implants. The following characteristics were considered when determining the risk factors: patient demographics (age and sex), overall health status , anatomy-related characteristics , implant-related characteristics , surgical procedure and prosthesis aspects .In all of the related studies, neither age nor sex was significantly associated with late failure ,13,15,16Two studies investigated the effect of radiation therapy on late failure ,21: AlsaControlled diabetes did not significantly influence the late implant failure rate ,19,20,21Three articles investigated other medical problems ,16,21. Dp < 0.01) [The influence of oral history on late failure was documented in three articles ,18,20. Rp = 0.061) [Several studies did not find any statistically significant association between late failure and smoking, suggesting that smoking alone does not increase the incidence of late implant failure ,19,20,21= 0.061) .p < 0.001) [p = 0.02) [p < 0.05) [p < 0.05) [The impact of localization on late failure was reported in numerous articles, but the results remain controversial. Alsaadi et al. found that implants placed in the maxilla had significantly higher rates of late failure than those placed in the mandible  . Moreove = 0.02) . In cont < 0.05)  and HR = < 0.05) . However < 0.05) ,16,17.p < 0.001) [p < 0.01) [Two studies indicated that placing an implant in the anterior or posterior region was not a significant risk factor for late failure ,17. Howe< 0.001) . Further < 0.01) .Two studies indicated that the bone status (osteoporosis or osteopenia) was not significantly associated with late failure ,21. TherWhile no significant association was found between the implant surface treatment and late failure ,17,21, ap = 0.029) [Three studies found no significant association between implant length and late failure ,20,21. A= 0.029) .Most of the studies found that implant diameter was not a significant risk factor for late failure ,17,23. OAll of the four studies related to surgery type found that bone augmentation was not a significant risk factor for late failure ,16,17,19Two studies related to the time of implantation produced different results ,22: Strip < 0.05) [Manor et al. reported that the rate of late failures did not vary significantly between different implant brands; they also found that bruxism did not significantly affect late failures . In cont < 0.05) . Noda et < 0.05) .This review has summarized the significant risk factors for late dental implant failure. It is clear that various local and systemic factors could damage the integrity of the osseointegration established around an implant after occlusal loading. The exposure of an implant and its suprastructure to the oral microbial environment and the application of occlusal forces make detecting the relevant factors more difficult. We propose categorizing the risk factors for late failures that we identified into three groups related to (1) the patient history, (2) clinical parameters and (3) decisions made by the doctor . This clMany patients seeking implant rehabilitation are of an advanced age, which increases the prevalence of systemic medical problems such as diabetes and osteoporosis. These disorders could exert harmful effects on bone metabolism and thereby endanger the integrity of osseointegration. Nonetheless, the results obtained in this review indicate that only radiation therapy could significantly increase the risk of late failure, but not sex, age or medical problems. Radiation therapy (including radiotherapy and radiochemotherapy) could compromise the oral environment so as to significantly increase the risk of late failure ,21. A prRegarding the oral history, a history of periodontitis is an important risk factor for late failure. Periodontitis is one of the main reasons for tooth loss that leads to a requirement for implant rehabilitation. Moreover, a previous review indicated that a history of periodontitis could be considered a predictor of peri-implantitis that could lead to late failure . Jemt etIt is particularly interesting that two studies found that all subjects with late loss also experienced at least one early loss ,28. AlthSmoking causes several local and systemic diseases and jeopardizes both bone and wound healing processes . DespiteBruxism seems to be as the most important risk factor endangering the implant survival rate . BruxismPlacing an implant in a posterior location was reported as a significant risk factor for late failure ,13,21, aDespite implant placement in the maxilla being found to be a significant risk factor for early failure , its infThe demand for implant placement is higher among elderly women since they are prone to greater osteopenia or osteoporosis. Although these bone metabolic diseases could have a negative impact on implant stability and have shown trends for more late failures, no significant associations between these bone conditions and late failure have been found ,21. NeitWhile the bone condition and bone volume did not significantly influence the rate of late failures of dental implant, a low bone density poses a significant threat to implant outcome. Low bone quality, especially type IV , was found to significantly increase both the late- and early-failure rates ,23. PoorOnly one study found that the presence of more than 20 remaining teeth could significantly increase the late failure rate . The reaRegarding the opposing dentition to dental implant, a partial or a complete removable denture was reported to be significant risk factors to late failure . The difTherefore, careful prosthesis planning and meticulous occlusal adjustment are mandatory for the implant long term success.Despite the implant design and surface treatment not significantly influencing late failure of dental implant, there was a tendency for implants with a machined surface to be associated with a higher failure rate . MoreoveIt is advisable to place a short implant when the bone height is inadequate. However, this strategy should be performed with caution in immediately loaded implants, for which short implants were associated with a significant decrease in implant success . The redAlsaadi et al. found an increased rate of late failure among large-diameter implants, but this could have been due to the surgeon being inexperienced or wide implants usually being employed as “rescue” implants . It shouWe found that the implant brand does not appear to significantly influence the late-failure rate, as also found by Manor et al. . In contThe investigations perform in this review suggest that the implant selected does not play an important role in late failure. However, clinicians should pay more attention in certain circumstances such as during implant placement with a surgical guide and immediately loaded implants.A two-stage surgical protocol has been recommended for implant placement since being introduced by Branemark ,3. HowevSeveral studies have shown that bone augmentation is not significantly associated with late failure. Moreover, implant placement with bone augmentation was found to be likely to have a higher success rate . This prA high Periotest value either during implant insertion or at the abutment connection was found to be a significant risk factor for late failure . This paIn addition to the above surgery-related considerations, patient postsurgery follow-up and compliance should also be considered. Most patients report signs of mucosal inflammation or irritation at the implant site before failure actually occurs. An early diagnosis of inflammation at the implant site during the first year was significantly associated with late failure (HR = 17.95) . Thus, pAn implant-supported overdenture provides several benefits over an implant-fixed prosthesis, such as being cheaper and ease of prosthesis maintenance. However, clinicians should avoid using a conus-type connection, which was reported as a significant risk factor for late failure . FurtherThis literature review has revealed more risk factors than the previous publication . Based oThe limitation of this literature review is the lack of a data meta-analysis. It is possible that further risk factors could be identified in future well-designed studies.


Using 2D-strain imaging, we measured LV longitudinal and circumferential (circ) strain (εsys), systolic strain rate (SRsys), early (SRe) and atrial (SRa) diastolic SR, LV electromechanical dyssynchrony (TTP-SD), and LV twist and torsion in study groups.We examined the impact of left anterior descending (LAD) wrapping on left ventricular (LV) mechanics in patients with normal coronary angiography. Seventy-one patients with evidence of normal coronary angiography (LAD wrapping: P < 0.0001), global longitudinal εsys % (P < 0.02), circ SRa at the basal segments (P < .02), circ SRsys and SRe, and SRa (P < 0.0001) at the apical segments and apical rotation compared with the non-wrapped group. LV twist was correlated negatively with LV electromechanical dyssynchrony  and positively with longitudinal εsys , circ εsys% , circ SRsys , and circ SRe . Using multivariate regression analysis, DT: OR 0.932, CI 0.877–0.991, and P < 0.02 and circ at atrial diastole (SRa): OR 0.000, CI .000–.271, and P < 0.03 were independent predictors of LAD wrapping around LV apex.No significant difference in age, gender, body surface area (BSA), or ejection fraction (EF%) between groups. LAD-wrapping group showed higher deceleration time (DT) (Wrapped LAD is associated with better myocardial relaxation and rotational mechanics in patients with normal coronary angiography. This could explain the worse prognosis in such population when LAD occlusion acutely emerges. Nowadays, coronary artery disease represents 31% of deaths and the most important cause of morbidity and mortality all over the world . Angiographic data was reviewed by at least two experienced observers.A normal coronary angiogram was defined as one with the absence of any identifiable pathology  . Entireln = 52) and those with the LAD terminating at or before the apex constituted .From 1600 patients who undergone elective angiography, 71 meet our inclusion criteria. The patients were categorized into two groups according to LAD anatomic feature: those with a long LAD (wrapping around LV apex) constituted  equipped with a multi-frequency 2.5–3.5 MHz phased-array transducer was employed. LV end-diastolic and systolic  diameters, septum (SPT) and posterior (PWT) wall thickness, LV mass (LVM), and LVM index (LVMI) were calculated in accordance with the recommendations of the American Society of Echocardiography . LV EF% Mitral inflow velocity patterns were recorded from apical 4CH view (4–5 mm) sample volume width was utilized to be placed at the mitral leaflet tips, in diastole and using 3 consecutive cardiac cycles. An optimized pulsed wave Doppler beam parallel to the direction of mitral inflow was taken. Peak early and late diastolic trans-mitral velocities (E&A) and E-wave deceleration time were measured. All pulsed Doppler signals were recorded at a horizontal sweep of 100 mm/s .LV diastolic function assessment was performed using conventional transmitral flow velocity-derived indices. Additionally, the mitral annular motion was recorded from the apical 4CH view using a tissue Doppler imaging program (TDI) . A 4–5-mBoth LV segmental and global mechanics were analyzed using vector velocity imaging (VVI). It is an angle-independent feature-tracking mode that encompasses speckle tracking with endocardial and epicardial contour tracking. It measures myocardial motion from B-mode clips by automatically tracing contours to define the inward and outward myocardial motion .sys, systolic SR (SRsys), early (SRe), and atrial (SRa) diastolic SR of the basal, mid, and apical segments at the mid myocardial layer of septal, lateral, anterior, and inferior walls were measured and averaged to calculate the global deformation. Circ εsys was measured from short-axis views at the mid papillary levels, midway between the mitral valve and the apex; LV twist was measured from short-axis views at the basal and apical levels; the basal short-axis plane contained the mitral valve; and the apical plane was acquired distally to the papillary muscle, as circular as possible and proximal to the plane with luminal obliteration at end-systole. LV twist was calculated as the instantaneous difference between apical and basal rotation , among LAD wrapping group, and 1.36 [11 (57.9%) males and 8 (42.1 %) females]. Patients with LAD wrapping have a higher prevalence of hypertension , lower prevalence of diabetes mellitus , and less prevalence of cigarette smoking  compared with LAD non-wrapping. No differences between patients groups in BSA, heart rate, blood pressure, or family history of CAD.Patient’s clinical characteristics were depicted in Table P < 0.003; LVMI: 115.5 ± 28 versus 92.9 ± 29, P < 0.004; and DT: 173.2 ± 38.3 versus 131.9 ± 29.8, P < 0.0001.There was no significant difference between the two groups in LV dimensions, LA dimension, EF%, or E/E' as demonstrated in Table sys) or systolic strain rate (SRsys) as demonstrated in Table There was no significant difference between LAD wrapping and LAD non-wrapping groups in segmental or global longitudinal strain , apical lateral (P < .005), apical anterior (P < .004), lateral, and inferior was significantly greater than non-wrapping group (P < .001). Consequently, the global atrial diastolic strain rate (SRa) was significantly higher in the LAD wrapping group compared with LAD non-wrapping group P < 0.02 , posterior , inferior , septum , and global levels .74 ± 1.14 vs .38 ± .08, P < .01. However, there was no significant difference in circumferential strain or SR during systole or early diastole , apical anterior rotation with P < .003, and the averaged degree of LV apical rotation (P < .003) compared with LAD non-wrapping group. These higher values of apical rotation resulted in augmented LV twist and LV torsion in LAD wrapping group compared with non-wrapping group , respectively , modest inverse correlation to LV dyssynchrony as estimated by TTP-SD , and direct correlation to LV systolic SR (SRsys) . Furthermore, the LV twist showed a strong direct correlation to diastolic function during early diastole as estimated by SRe . Considering circumferential strain, LV twist showed a strong direct correlation to both basal  and apical rotation degree   Fig. . No signa, circumferential εsys circ SRsys, circ SRe, circ SRa, apical rotation, and LV twist to discriminate LAD wrapping from LAD non-wrapping. From all these variables, LVMI , DT , global longitudinal SRa , and LV apical rotation  were independent predictors for LAD wrapping around LV apex in angiographically normal coronary arteries.Variables that were statistically significant in univariate analysis were introduced in a forward logistic regression model to estimate the independent predictors of LAD wrapping; these include hypertension diabetes mellitus, smoking, LVMI, DT, longitudinal SRIn the current study, we demonstrated that in patients with angiographically normal coronary arteries, long LAD that wrapped around LV apex ensured better longitudinal relaxation during late diastole, higher circumferential deformation at the LV apex, and augmented apical rotational mechanics. This deformational changes were resulting in higher LV twist despite no difference in LV ejection fraction measured by conventional methods. Longitudinal deformation in late diastole and LV apical rotation are independent predictors of LAD wrapping around LV apex in the presence of normal coronary circulation.The present study is the first study, up to our knowledge, that investigated the relationship between LAD coronary artery anatomical features and cardiac mechanics in patients with angiographically normal coronary arteries.Evaluation of LV function using 2D Echo-Doppler primarily is unable to describe detailed information about cardiac mechanics, specifically when there are no coronary arterial or structural heart diseases. Strain imaging using VVI is a semi-automated technique that is more precise and accurate in characterizing LV function than the conventional methods.Additionally, as distinct from previous studies, in our study, measurements of longitudinal and circumferential strain incorporated specifically the mid myocardial layer which reflecting the true regional function allowing an early detection of subtle myocardial abnormalities , 19.Lately published researches verified the crucial value of global longitudinal strain (GLS) as an important functional parameter that provides imperative diagnostic and prognostic information in patients presented with acute coronary syndromes , 22, andn = 871) and group 2: LAD non-wrapping (n = 224). They demonstrated that heart failure, significant arrhythmias, and LV mural thrombi were more common in the wrap-around LAD group. Additionally, LV ejection fraction was worse in the wrap-around LAD group . Thereafter 3 years of follow-up, major adverse cardiac events  were higher ; death , stroke , stent thrombosis , and severe heart failure  were more prevalent in wrap-around LAD versus non-wrap-around LAD. Multivariate regression analysis revealed that LAD wrapping independently and considerably anticipated the occurrence of adverse cardiovascular events and severe heart failure in patients with an anterior STEMI.Kobayashi et al. , 10 inveIn the current study, we perceived the explanation of different patient outcomes when LAD obstruction, with wrap-around apex, coexist as there is more loss of augmented function especially at LV apex; the LAD wrapping group had better mechanics and higher longitudinal relaxation. In addition, the main difference between wrapping and non-wrapping LAD groups is the higher circumferential function and augmented apical rotation that result in increased LV twist. So, not only a larger area of myocardium becomes vulnerable but a significant mechanical dysfunction is added when LAD obstruction supervenes, if LAD wraps around the apex.Patients with proximal LAD occlusion are recognized by cardiac surgeons and cardiologists as a high-risk group with increased morbidity and mortality. However, not all proximal LAD lesions are of the same clinical relevance. Forty percent of LV myocardium is supplied by LAD, including the anterior wall and the anterior segment of the interventricular septum . The LADsystole, the LV undergoes a unique twist motion with a counterclockwise rotation at the apex and a clockwise rotation at the base. The resulting twist during peak systole is 7.7 ± 3.5° [During 7 ± 3.5° . This is7 ± 3.5° . EventuaIn our study, LV apical rotation and overall LV twist are much lower in LAD non-wrapping, and the larger part of LV twist is generated from apical counterclockwise rotation, so the peak LV twist is predominantly reduced in apical myocardial infarction; this might explain the reduction of LV torsion and even the occurrence of an apical aneurysm in apical myocardial infarction , 29.Yet, in the present study, longitudinal strain did not differ between the study groups, and the longitudinal strain caused by the contraction of myocardial tissue in the endocardial layer and has a high sensitivity to myocardial ischemia which does not exist in our patients with angiographically normal coronaries. Several studies demonstrated that global longitudinal strain is a more sensitive and robust parameter for evaluating myocardial function compared to circumferential and radial strain , 31, whia and SRe) was enhanced in a patient with long LAD that wraps around the apex. The underlying mechanism was reported in Wang et al.’s research [In addition, our study demonstrated that the left ventricular diastolic function as measured by deceleration time, longitudinal and circumferential strain, and strain rate during diastole  had higher values of LV function especially during diastole. From previous studies, LAD has a major impact on prognosis in patients undergoing primary PCI. This is probably as a result of a greater amount of the muscle supplied by this type of LAD, and therefore, a greater amount of myocardial necrosis when the vessel totally occludes , 10. FurNotably, our study showed a strong positive correlation between the LV twist and longitudinal and circumferential strain and strain rate especially at LV apex, and this explains the augmented LV twist in the LAD wrapping group was associated with better circumferential strain values compared to the LAD non-wrapping group. We could expect that proximal LAD stenosis in such a group with LAD wrapping to further deteriorate LV function to a greater extent and recommend utilization of longitudinal and circumferential strain as an early marker of LAD stenosis that better reflect LV dysfunction than LV EF%. This is in agreement with Stokke et al.  who repoThere are numerous factors such as age, sex, diabetes mellitus, and hypertension that can affect cardiac mechanics in our study population, as examined by longitudinal and circumferential strain. Tadic et al.  demonstr2 close to the normal values. Moreover, previous investigators reported that the longitudinal LV strain is decreased in patients with hypertension [We included a real-life patient’s population with a variable risk profile who was referred to the catheterization laboratory for coronary angiography. However, we thought that the impact of these risk factors on cardiac mechanics might be equivalent. In the LAD wrapping group, hypertension was prevalent in 60% while diabetes mellitus and smoking were prevalent in 100% and 46% in LAD non-wrapping which represents a balanced exposure to cardiovascular risk. Compensatory left ventricular hypertrophy was existent in only 35% of the LAD wrapping group which renders their LVMI 115 g/mrtension , 36 wherThe present study has several limitations. First, it is a small sample-sized study with a limited number of patients; however, it can be explained by the strict exclusion criteria and single-center study. Second, image acquisition and analysis depend on many factors including image quality, operator experience especially with strain analysis software, and vendor variability. Third, concurrent risk factors like diabetes and hypertension might influence data results, despite invasive detection of LAD anatomical features in a healthy individual may be challenging. Finally, long-term follow-up could be performed to obtain clinical and prognostic figures especially when LAD obstruction occurs. Thus, large scale, multicenter, prospective, trials with enough power to examine the effect of all confounding factors are required to overcome these limitations.LAD wrapping around LV apex is a characteristic anatomical feature of coronary circulation that provides better myocardial relaxation, augmented circumferential, and rotational mechanics contrast to non-wrapping feature, in patients with normal coronary angiography. This could explain the poor prognosis and worse outcome in such population when acute LAD occlusion supervenes.


Echocardiography, as a feasible tool used to evaluate the cardiac functions, is relatively expanded in the literature of goat’s research because of being a reproducible animal exemplary for cardiovascular research. However, previous studies do not fully describe the full echocardiographic protocol including tissue Doppler imaging (TDI) in goats, the same as used in pet animals, and it was rather mainly focusing on females than males despite its importance for studying the flow dynamics in ruminants. The clinical utility of echocardiography in farm animal practice is still limited and mainly utilized for research purposes. Consequently, the culling strategy of diseased animals suffering from cardiac disorders is usually prioritized more than treatment because of lacking the precise diagnosis of the problem. Breed-specific variations in the echocardiographic measurements may occur and there are no previous study documents the echocardiographic interval parameters in Shiba goats, a native breed in Japan. In the current study, we investigated the feasibility of the full conventional echocardiography protocol as used in companion animal practice and reported for the first time the TDI indices in male goats to provide valuable reference data that can be used for either research or clinical cardiology application in goats. We further highlighted the echocardiographic changes after sedation with xylazine, a common anesthetic medication used in ruminants, as a guide to veterinarians under field conditions.p < 0.05). For TDI, the Post-Xyl group revealed a significant decrease in the myocardial velocities of the septal and lateral wall of the left ventricle. The present study provides, for the first time, complete data of conventional echocardiography in male goats using the full protocol, which is routinely used in pet’s practice. Further, we illustrate in-depth the adverse effect of short-term sedative, xylazine, as used under field conditions and emphasize a simultaneous reduction in both systolic and diastolic cardiac function in goats based on full echocardiography assessment of the heart.The present study aimed to provide a complete conventional echocardiographic protocol in adult male Shiba goats by using two-dimensional, M-mode, Pulsed Wave Doppler, and tissue Doppler imaging (TDI) echocardiography, and to study concomitantly xylazine-induced alteration of cardiac functions in a highly sensitive species. For this purpose, 12 male Shiba goats were included and complete conventional echocardiography from the standard right and left parasternal views was carried to report the echocardiographic data in male Shiba goats, and also before and after xylazine (Pre-Xyl and Post-Xyl) administration (0.05 mg/IM/kg). Results revealed that the full echocardiographic protocol was feasible in all goats through different cardiac windows and good Doppler alignment was achieved with non-significant variability for assessment of the left ventricular dimensions, trans-pulmonary, trans-aortic, and trans-mitral blood flow. The TDI, which was not reported previously in goats, was successfully assessed from the standard left apical view and showed distinct systolic and diastolic patterns. Xylazine administration was found to significantly reduce heart rate, fractional shortening, and cardiac output as well as the Doppler hemodynamic parameters of the pulmonary artery, aortic and mitral inflows ( Long-lasting ago, echocardiography became the gold standard and a routine tool used for the diagnostic evaluation of cardiovascular upsets in humans and animals. It also provides non-invasive and reliable landmarks necessary to assess the efficacy, safety, and viability of drugs and the potential risks of their use . NowadayGoat’s echocardiography was reported for the first time by Gardner et al.  after thUnlike female goats, quantitative echocardiography in males did not fully described and only two of the aforementioned literature have been conducted in a large group of sheep and goats including male goats without paying any attention to male reference intervals ,21. BesiUnder field conditions, xylazine is the most widely used tranquilizer in ruminants for invasive surgery and controlling of seizure animals during examination and transportation. The drug has brought abrupt changes in the cardiopulmonary function including a reduction in the heart rate, respiratory rate, and cardiac output and inducing fluctuation of blood pressure and oxygen tension. These changes have been selectively studied through intra-arterial catheterization, blood gas analysis, M-mode echocardiography, and electrocardiography in different animal species including cattle , donkey All experimental procedures and animal care were followed the guidelines established by the local committee belonging to the Tokyo University of Agriculture and Technology, Japan  for the use of animals in experimental studies .Twelve adult male Shiba goats, 24–28 months old, and 30 ± 3 kg body weight (BW) were enrolled in this study. Goats were housed in a special barn that belongs to the Laboratory of Veterinary Physiology, Tokyo University of Agriculture, Japan, where they received 0.6 kg of hay cubes as a basic diet twice daily and water and trace minerals were kept ad libitum. Detailed physical examination was performed and animals were considered physically fit based on the medical record, auscultation of the heart, electrocardiography and echocardiography, and routine hemato-biochemical profile. In all goats, findings of clinical examination and hemato-biochemical parameters determined before the experiment fell within relevant reference intervals characteristic for the species .The experiment was conducted to record the normal reference echocardiographic data in male goats as well as before and after sedation with xylazine  using a standard dose  without any surgical interference according to Grant and Upton . FirstlyThe echocardiography was conducted for wake goats twice at a one-day interval by the same observer to record the full conventional echocardiographic reference data. In the next week, the procedures were repeated twice at a one-day interval to record the echocardiographic data before and after the administration of xylazine. The average of the recorded measurements was obtained from five repeated cardiac cycles. The echocardiographic examination was carried out while animals were restraint by two assistants on a special echocardiographic examination worktable in the lateral recumbency and the forelegs were holding anteriorly as much tolerated by the animal. The right and left precordial areas were shaved and coated with an ultrasonic coupling gel. A ProSound F75 premier CV ultrasonography system  supplied with a sector probe of 5 MHz and an electrocardiographic monitoring system was used. The time required from each echocardiographic view was reported. The recorded measurements and image orientation were following the American Society of Echocardiography guidelines .v) and late (Av) velocities, Ev/Av ratio, and deceleration time (DecT) were obtained from the trans-mitral flow profile using PWDE. Also, the transducer was slightly moved anteriorly to obtain the left apical 5-chamber view for Doppler evaluation of the trans-aortic blood flow.A full conventional two-dimensional, M-mode, and Doppler echocardiography from the standard right and left parasternal views was performed on each animal according to the methods described by De Madron, et al. . FirstlyThe following Doppler parameters of the pulmonary and aortic flow has been addressed: peak velocity (PV), pressure gradient (PG), mean velocity (MnV), mean pressure gradient (MPG), velocity-time integral (VTI), right ventricular outflow tract (RVOT), left ventricular outflow tract (LVOT), the cross-sectional area of the artery (CSA), pre-ejection time (PEP), ejection time (ET), and acceleration time (ACCT).m) and diastolic indices  at the point of attachment of the mitral valve to the septal and lateral walls of the LV. The average TDI parameters as well as the ratio between the early diastolic mitral inflow (Ev) and diastolic velocity (Em) of the septal and lateral walls of the LV (Ev/Em) were calculated. From the left apical 4-chamber view, the tissue Doppler imaging (TDI) of the lateral and septal left ventricular wall was reported by using pulsed-wave TDI echocardiography according to De Madron, et al. . The samp < 0.05, and data are expressed as Mean ± SEM. For the non-gaussian data which showed a significant KS test, the Mann Whitney test for non-parametric data was used and the median was considered. All statistical analysis was carried out using GraphPad Prism 6.0 . The normality test for variable distribution was assessed using the Kolmogorov-Smirnov (KS) test and the coefficient of variations (CV%) between days was calculated. The Paired t-test was used to analyze the significance before and after xylazine administration, with a probability of p = 0.02) and HR  were observed after 12 min of xylazine administration.All animals showed prominent signs of sedation 10–15 min after I/M injection including head dropping, ataxia, and limb crossing, hypotonia and hyporeflexia, and mild ruminal bloat. A significant reduction in the respiratory rate . However, the PV, MPG, PEP/ET, and ACCT/ET of the aortic and pulmonary Doppler flow, as well as the Sm of septal TDI and Am of lateral TDI showed non-Gaussian (p < 0.05). The age and BW of goats were normally distributed (p > 0.05) with a mean of 26 months and 30 kg, respectively. The CV% for the obtained echocardiographic parameters ranged between 6.6–43%. The data were further classified according to CV% into low , moderate , and high  variability. The intra-observer variability of the echocardiographic data, which has been assessed in all goats before xylazine administration showed a non-significance difference (p > 0.05). Interestingly, the p-value of all tested parameters was exceeding p = 0.10. However, certain measurable parameters including AoDd, HR, aortic PV, PG, PEP were trend (p = 0.06–0.09).During the echocardiography examination, no obvious abnormality has been detected in all goats; therefore, all obtained animals have been included in the statistical analysis. The normality test revealed a normal distribution of the majority of the data  in the Post-Xyl group comparing with the Pre-Xyl group. Left ventricular FS% showed trend reduction (p = 0.06) meanwhile the EF% did not change between groups  and aortic Doppler parameters  were significantly reduced compared with the Pre-Xyl group (p < 0.05) as shown in The spectral pattern of the mitral inflow showed variation before and after xylazine administration. In the Pre-Xyl group, the E and A waves were fused in 50% of goats (6 goats), and the Em) and two retrograde diastolic waves (Em and Am)  . Althougm, Em, and Am of the lateral wall was greater than the septal one , respectively. In the Post-Xyl group, there was a significant reduction in the Sm, Am and Em/Am  and trend Ev/Em (p = 0.06) of the septal TDI; reduced Sm and Em  and trend Am (p = 0.06) of the lateral TDI; reduced Sm and Am , and trend Em (p = 0.06) of the averaged TDI compared with the Pre-Xyl group.In cardiology research, the precise details of the heart functions in goats are crucial for the incorporation of the technique into the veterinary practice as well as for effective modeling of cardiology research. In the present study, a full echocardiographic protocol was performed to provide reliable data of the systolic, diastolic, and regional myocardial functions in male Shiba goats, and to explore the detailed impact of xylazine administration on cardiac measurements. Unlike dogs and cats, literature successfully conducts the echocardiography in goats is limited. The presence of an accessory lung right lobe that partially obscuring the heart, gas-filled rumen against the diaphragm, the vertical orientation of the heart, and a large and thick sternum are the main obstacles to obtain good quality images during echocardiography in sheep and goats ,36,37. OImportantly, few studies are focusing on goat’s echocardiography in which female goats, particularly the Saanen breed, are the most studied animal ,13. MeanIn the present study, the reported echocardiographic indices are in good agreement with previously reported indices of LV M-mode echocardiography of Saanen goats with an average BW of 66 ± 9 kg ,21 and gm, movement of the mitral annulus toward the cardiac apex) and two negative diastolic velocities; Em and Am, which are related to myocardial relaxation and atrial contraction, respectively. Unfortunately, there are no data in the previously cited studies in ruminant species to compare the TDI with our results. In sheep, the TDI was previously obtained from RPSAV at the mitral valve level [v was higher than Av, and the Em was higher than Am in both groups. Meanwhile, reduced myocardial contractility and HR were observed in the Post-Xyl group with unfused mitral inflow E and A waves. This could be attributed to the direct negative chronotropic effect of xylazine, which results in the reduction of myocardial contractility, mitral inflow, and TDI parameters [TDI is widely used in canine and feline as well as human cardiology to assess the global and regional wall motion velocity during systole and diastole at the two points of the mitral annulus and independently from loading conditions ,45. To tve level . In the ve level , and rabve level ,48. The rameters ,50 and tm velocity is negatively correlated with early diastolic pressure thereby considered as an indicator for relaxation and elastic recoil of the LV. Likewise, the elevation of the LV filling pressure results in increased mitral Ev and concomitant reduction in Em. Meanwhile, the Ev/Em ratio is of particular value to interpret the congestive states since it correlates well with the LV end-diastolic pressure or pulmonary capillary wedge pressure [v/Em and Em/Am is indicative of congestion when exceeding 15 and 1.5, respectively in dogs and cats [The mitral inflow and TDI velocities are useful indices for the interpretation of the diastolic function . Generalpressure . Practicand cats  but therv and Av were significantly reduced in the Post-Xyl group  compared with the Pre-Xyl group  with approximately the same value which results in a non-significant change in the E/A ratio. Also, xylazine administration significantly reduced the atrial contractility as observed by a significant reduction in Av and Am. The net effect of xylazine on systolic and diastolic functions of the LV might depend on its ability to induce changes in preload, afterload, contractility, and heart rate. Therefore, the reduction in systolic FS and maintenance of CO after xylazine administration might be attributed to alterations in loading conditions and the chronotropic activity [To the best of our knowledge, there has been in international literature no reporting quantitative echocardiographic data in awake versus tranquilized goats using our approach. Xylazine, as a gold standard α2 agonist, is the most trustworthy drug used in farm animal practice for sedative and analgesic purposes . In the activity ,53.In the present work, some potential limitations deserve attention. We did not compare our results with those reported in female goats because of the difference in the used procedures and protocol. For example, some studies monitor only the LV function by M-mode , others The present work provides, for the first time, a detailed description of echocardiographic measurements in healthy male Shiba goats by using various echocardiographic techniques including 2-D, M-mode, Doppler Echocardiography, and pulsed TDI. This is considered a promising step forward of the used echocardiographic approaches for diagnostic and prognostic evaluation of cardiac functions in goats for further clinical and research purposes. Besides, we highlighted the effect of xylazine administration on cardiac parameters in goats that revealed a rapid reduction in the cardiac parameters even under the recommended dosing.


An increase in pulmonary artery pressure (PAP) leads to secondary right ventricular (RV) failure. In patients with PAH, the development of heart failure is an indicator of a poor prognosis.Pulmonary arterial hypertension (PAH) is one of the most important and potentially fatal alterations to the pulmonary circulation; if it goes untreated, it is associated with high morbidity, high mortality, and a poor prognosisIn the last decade, various studies have highlighted the importance of imaging methods other than angiography in the evaluation of pulmonary artery disease. One of the most widely used of such methods is cardiac magnetic resonance imaging (MRI).. It has several advantages over other methods, mainly due to its noninvasive nature and its capacity to evaluate, in only one examination, morphology, RV function, left ventricular (LV) function, and tissue characteristics, as well as to provide functional information by perfusion imaging at rest, pharmacological stress testing, and flow studies.For the evaluation of systolic function and the quantification of cavity volumes, as well as of the myocardial mass, cardiac MRI is considered the gold standard. The maximum angle of septal excursion toward the LV in ventricular systole-the interventricular septal angle (α)-also shows a strong correlation with PAP determined by invasive techniques.Flow cardiac MRI studies can provide several noninvasive measurements that reflect the hemodynamics of the pulmonary arterial system. For example, curvature of the ventricular septum is strongly correlated with an RV > LV pressure gradient and is comparable to RV systolic pressure determined by catheterization. The mean PAP estimated thusly has a sensitivity of 87% and a specificity of 90% for the diagnosis of PAP > 32 mmHg. Pulmonary artery flow velocity has also been shown to correlate with the mean PAP.The mean PAP and pulmonary vascular resistance can also be estimated by cardiac MRI with regression equations.Other variables evaluated in PAH include: the relative change in area; increase in the maximum peak velocity; the time to maximum velocity; the maximum change in flow at ejection time; increase in the oscillatory shear index; increase in the shear interval; the transpulmonary gradient in the pulmonary artery; transmitral flow; myocardial tissue velocity; left atrial volume; and left atrial flow.In addition to all the information provided above, cardiac MRI allows prognostic factors to be estimated and risk to be stratified. For example, delayed myocardial enhancement volume correlates with RV mass, RV volume, RV dysfunction, RV remodeling, and septal curvature, indicating a poorer prognosisRadiologia Brasileira, readers will find an interesting article authored by Mello et al., who studied the relationship between the right atrium area and the RV ejection fraction by MRI, in comparison with other prognostic markers, in patients with PAH. In their study, the authors found that the RV ejection fraction and the right atrium area determined by cardiac MRI both correlated with clinical prognostic markers. However, they showed that the RV ejection fraction showed stronger and more significant correlations than did the right atrium area.In this issue of


The beneficial effect of physical activity (PA) on the brain has been well established. Both acute and regular PA can boost a range of cognitive functions and enhance mood and mental health. Notably, the effect of acute PA on the brain and cognitive functions is generally found to be dose-dependent, in terms of both the amount and intensity of the exercise episode. In contrast, in the case of regular PA, the literature has primarily focused on the amount of exercise, and limited studies have assessed the influence of the exercise intensity. Since PA in higher intensity causes more extensive, more powerful, and longer-lasting neurobiological changes, it may prove more beneficial to cognitive functions and mental health. In the present study, we set out to test this hypothesis by employing a battery of questionnaires and laboratory tests with a sample of young adults. We found that more frequent vigorous- and moderate-intensity PA rather than walking (considered low to moderate intensity) was associated with better cognitive and mental health measures. Meanwhile, compared with no moderate- to vigorous-intensity physical activity (MVPA) at all, as few as 1~2 days per week (lasting at least 10 min each time) of MVPA was associated with a variety of benefits, particularly related to coping with challenging situations. In light of the neurobiological literature, the present study speaks to the value of moderate- to vigorous- rather than low-intensity PA in enhancing cognitive functions and mental health. The beneficial effect of physical exercise or physical activity (PA) on the brain has been well established. Both acute and regular PA can boost a range of cognitive functions and enhance mood and mental health ,2,3,4,5.Furthermore, the beneficial effect of PA is generally considered dose-dependent, such that greater amount and higher intensity of exercise is associated with more enhanced outcomes, for instance, cognitive functions . HoweverSince PA performed in higher intensity causes more extensive, more powerful, and longer-lasting neurobiological changes, it may prove more beneficial to brain functions. Indeed, a single bout of vigorous- rather than low-intensity cycling has been reported to increase the peripheral level of brain-derived neurotrophic factor (BDNF) . BDNF isTherefore, we hypothesized that frequent PA at moderate and vigorous rather than low intensity exerts greater benefit to cognitive functions and mental health. In the present study, we set out to test this hypothesis in a sample of young adults using a battery of questionnaires and laboratory tests. Investigating this hypothesis also allows us to propose more specific recommendations or guidelines for public health promotion in young adults.This research was part of a larger study, the aim of which was to predict mental health status using high-level brain functions. Data collected at baseline of the study were used for analysis here. The study was approved by the Institutional Review Board of Yamaguchi University Hospital . Participants were recruited via numerous posters displayed in the university community. The inclusion criteria were being 20–39 years old at the time of the visit, and the exclusion criteria were (a) having any self-reported mental health diseases, (b) receiving medical examinations due to suspicion of any mental health diseases, (c) being suspected of mental health diseases by the research staff and then diagnosed as having a mental health disease by the Mini-International Neuropsychiatric Interview conducted by a psychiatrist, or (d) being unable to answer the questionnaires and perform the laboratory tests for this study due to severe physical conditions or other reasons. Fifty-eight subjects agreed to participate in this study and provided written informed consent after receiving a detailed explanation of the study.Subjects first answered questions about their demographic characteristics, including gender, age, occupation, and educational level.To evaluate PA, we used the short-form International Physical Activity Questionnaire (IPAQ) . IPAQ meIn the present study, we employed two different methods generated by the IPAQ to evaluate PA. First, we categorized the participants into one of three levels of PA, Low, Moderate, or High, based on one summary indicator, total weekly PA Metabolic Equivalents , as suggested by the developers of the IPAQ. Total PA was calculated by weighting the reported minutes per week within each activity category by a MET energy expenditure estimate assigned to each activity category . High PA level is defined as meeting either of two criteria: (a) vigorous intensity activity on >3 days/week and accumulating at least 1500 MET-minutes/week; or (b) >7 days of any combination of walking, moderate-intensity, or vigorous-intensity PA achieving at least 3000 MET-minutes/week. Moderate PA level is defined as meeting any of the following three criteria: (a) 3 days of vigorous-intensity activity of at least 20 min/day; (b) 5 days of moderate-intensity activity or walking of >30 min/day; or (c) 5 days of any combination of walking, moderate-intensity or vigorous-intensity PA achieving at least 600 MET-minutes/week. Those who neither meet the Moderate nor the High criteria were categorized as Low PA level.Second, we employed the intensity-specific frequency, that is, the number of days per week performing activities at each intensity, respectively, in our analysis. Although the first method of evaluating PA  has been widely used in the literature, it is actually not a very good representative of exercise intensity. Subjects who walk and do moderate PA several days a week and much time each day without doing much vigorous activity can be categorized to High PA level. Therefore, to differentiate the effect of PA at different intensities, we also employed the intensity-specific frequency in our analysis. Another strength of this method is that it allows us to give specific recommendations about the minimum days of intensity-specific PA per week that can bring cognitive and/or mental benefits, the approach of which has been frequently employed in the literature ,20. To gCreativity. We used a paper-based quiz composed of insight tasks to evaluate creativity. This included two matchstick arithmetic problems [problems , the ninproblems . SubjectWorking memory. We used a computer-based n-back task  to assess working memory. The task was programed by Jörn Alexander Quent after [d) and response time (in ms) were used for data analysis.nt after  using MAnt after ). In thint after . The disMindful attention. We used the Japanese version [ version  of the M version . The MAATrait measures: the following trait-like dimensions of mental health were evaluated.Emotional contagion. We used the Japanese version [ version  of the E version , a 15-itEmotion regulation. We used the Japanese version [ version  of the E version , a 10-itCoping. We used the Japanese version [ version  of the B version , a 28-itBehavioral inhibition and behavioral activation. We used the Japanese version [ version  of the B version , a 24-itTrait anxiety: We used the Y-2 subscale of the Japanese version of the State–Trait Anxiety Inventory (STAI) to assess trait anxiety. Note that the two subscales of the STAI were administered together following Depression, see below.State measures: the following state-like dimensions of mental health were evaluated.Depression. We used the Japanese version [ version  of the B version , a 21-itState anxiety. We used the Y-1 subscale of the Japanese version [ version  of the S version , a 40-itPerceived stress. We used the Japanese version [ version  of the P version , a 10-itPsychological wellbeing. We used the Japanese version [ version  of the R version , an 84-it-test was used to compare differences between two groups means. The level of statistical significance was set at p < 0.05.The statistical analysis was done with IBM SPSS Statistics 25.0  and MATLAB R2018b . Pearson correlation analysis was used to evaluate associations between exercise measures  and other variables . The Chi-square test was used to evaluate whether there was an association between PA level and gender and between PA levels and the two frequencies of MVPA. Linear regression was used to evaluate to what extent exercise measures can predict outcome variables, with or without adjusting for covariates such as gender and age. One-way Analysis of Variance (ANOVA) was used to determine whether there were any differences in outcome variables between subjects at the three PA levels , with or without gender and age as covariates . Bonferroni adjustment was used for post hoc comparison. Student’s The sample consisted of 24 male and 34 female subjects, with a mean age of 22.4 years (standard deviation (SD) 2.40 years). Fifty-six (98.3%) were undergraduate students, 1 was a graduate student, and 1 was working in a hospital as a healthcare provider. Regarding PA, cognitive functions, and mental health, the score (Mean ± SD) of each measure is shown in p < 0.01). No other significant difference in or association with exercise measures was found for gender and age  and behavioral disengagement  = 4.90, p = 0.011) for coping, BAS drive  = 6.66, p = 0.003), and personal growth  = 3.71, p = 0.031) of psychological wellbeing. As shown in p < 0.05). Similarly, compared with those at Moderate PA level, subjects at High PA level had a significant higher level of BAS drive (p < 0.05). PA level-wise scatter plots of other nonsignificant outcome variables are available in We first compared the outcome variables across different PA levels using one-way ANOVA and found four significant differences: active coping  = 3.91, p = 0.033 for the model, F = 4.69, p = 0.013 for PA levels), BAS drive  = 4.10, p = 0.006 for the model, F = 7.74, p = 0.001 for PA levels), and personal growth  = 3.97, p = 0.007 for the model, F = 4.85, p = 0.012 for PA levels) across the three PA levels remained significant after controlling gender and age by fitting a general linear model.The group difference for behavioral disengagement  = 2.84, p < 0.05). More days of walking was associated with fewer days of vigorous-intensity activity per week. Given this correlation, we next entered the frequency of each intensity activity into a linear regression model to determine what intensity activities contribute to the outcome variables while controlling other intensity activities.We confirmed there was a significant correlation between the frequency of walking and the frequency of vigorous-intensity activity  and including gender and age as covariates (Model 2). Model 1 could significantly predict six outcome variables, including 2-back Therefore, higher frequency  of vigorous-intensity PA predicts more active coping, less behavioral disengagement, greater autonomy, and increased personal growth. Whereas higher frequency of moderate intensity PA predicts less behavioral disengagement, higher frequency of walking predicts more denial with a trend towards significance. Notably, in predicting personal growth, the standardized coefficient of the frequency of vigorous intensity PA was bigger than that of age (0.404 vs. 0.270). The results of other nonsignificant outcome variables for model 1 and model 2 are shown in To give the general public specific recommendations, we created another measure, that is, the frequency of MVPA. The number of subjects conducting 0 to 7 days of MVPA per week was 13, 7, 9, 6, 9, 6, 5, and 3 in that order.We first checked the correlation between the frequency of MVPA and outcome variables, and the results are shown in p = 0.840). Nor did they differ in their proportion of different PA levels (χ² (2) = 0.842, p = 0.656).As the association between the frequency of MVPA and outcome variables seems linear, we next asked what is the minimum days that subjects have to conduct MVPA per week in order to make a difference in any outcome variables. As the number of subjects conducting 0 to 7 days of MVPA per week was 13, 7, 9, 6, 9, 6, 5, and 3 in that order, we combined subjects conducting 1 and 2 days of MVPA per week to a single group  and compared it with subjects conducting 0 days of MVPA per week (n = 13). As shown in On average, subjects conducting 1~2 days of MVPA per week did 0.50 ± 0.63 days of vigorous-intensity PA (45.63 ± 67.13 min/day), 1.06 ± 0.85 days of moderate-intensity PA (66.25 ± 69.37 min/day), and 3.75 ± 1.92 days of walking (59.06 ± 62.96 min/day). In contrast, subjects conducting 0 days of MVPA per week walked 4.77 ± 2.62 days per week .t-test. Outcome variables that demonstrated a significant between-group difference (p < 0.05) were plotted in We then compared the outcome variables of these two groups using Student’s In the present study, we employed two different methods to evaluate PA, PA levels and intensity-specific frequency. Our results showed that compared with those at Low PA level, subjects at High PA level used active coping more often and behavioral disengagement less often, and demonstrated greater drive for rewards and more advanced personal growth. Most of these results, except active coping, remained significant after controlling gender and age. These results suggest that a greater amount of PA is associated with more matured psychological coping strategies in the face of negative situations ,56, enhaHowever, the categorization of PA levels based on the proposed criteria is not without its limitations. As we have introduced, High PA level is defined as meeting either of two criteria: (a) vigorous-intensity activity on >3 days/week and accumulating at least 1500 MET-minutes/week; or (b) >7 days of any combination of walking, moderate-intensity, or vigorous-intensity PA achieving at least 3000 MET-minutes/week. From the categorization criteria, we could infer that vigorous-intensity PA in particular may be responsible for the above benefits, although one cannot be sure if that is the case. Individuals may be categorized as High PA level simply due to their greater amount of moderate-intensity PA and walking, with few vigorous-intensity PA. In other words, we cannot tease apart the contribution of PA at different intensities. This limitation is further emphasized by our observation that the frequency of walking is negatively associated with that of vigorous-intensity PA. Therefore, the sensitivity of PA levels in capturing the true amount of PA may have been compromised and confounded by combining the measure of walking with that of vigorous-intensity PA. In order to investigate what intensity PA contributes greater benefits, it is necessary to employ intensity-specific measures.For this purpose, in the present study, we employed intensity-specific frequencies, that is, days conducting one specific intensity of PA per week. After controlling gender and age, we found it was vigorous-intensity PA that brought various psychological benefits. More frequent vigorous-intensity PA was associated with more frequent use of active coping and fewer use of behavioral disengagement for coping with challenging situations. It was also associated with greater self-perceived autonomy and personal growth. Notably, in predicting personal growth, the contribution of the frequency of vigorous-intensity PA was much bigger than that of age (standardized coefficient 0.404 vs. 0.270). More frequent moderate-intensity PA was also associated with fewer use of behavioral disengagement. In contrast, the frequency of walking was not associated with any of the outcome variables we investigated.These results confirm our hypothesis and are consistent with the neurobiological literature that moderate- to vigorous- rather than low-intensity PA causes extensive, powerful, and long-lasting physiological changes, which account for the cognitive and psychological enhancing effects of PA ,26,27. TTo give the general public specific recommendations on the frequency of PA, we combined the frequency of moderate and vigorous intensity PA and created a new measure, the frequency of MVPA. With MVPA, we observed significant associations with cognitive functions and state anxiety. Thus, individuals with more frequent MVPA performed better on a 2-back working memory task. They could better differentiate targets from non-targets. Meanwhile, they also demonstrated fewer symptoms of state anxiety. These results are in line with a large amount of reports that PA conducted regularly enhances cognitive functions and mental health ,14,15,16We next compared subjects who conducted 1~2 days per week (lasting at least 10 minutes each time) of MVPA with those with no MVPA to investigate whether this minimum frequency of MVPA can bring any cognitive and/or mental health benefits. Compared with those with no MVPA, we found that subjects conducting 1~2 days of MVPA were more easily affected by happiness, more likely to use reappraisal for emotion regulation, more likely to use active coping, positive reframing, and religion, and less likely to use behavioral disengagement for dealing with challenging situations. In other words, mere 1~2 days of MVPA per week may bring people more positive emotions and more mature coping strategies ,56,60.Note that subjects conducting 1~2 days of MVPA did not differ from those conducting no MVPA in terms of their total PA (MET-minutes/week) or proportion of different PA levels. This again supports the argument that rather than the total amount, more intense PA is preferred. In our study, on average, subjects conducting 1~2 days of MVPA did 0.5 days × 45.63 min/day = 22.82 min of vigorous- and 1.06 days × 66.25 min/day = 70.23 min of moderate-intensity PA per week. This amount of PA is below the level recommended by the World Health Organization for adults  of doingA limitation of our study is the employment of the short- instead of the full-form IPAQ to evaluate PA. Consequently, we could not make differentiation of various PA domains, that is, PA conducted during work versus during transportation, for housework, or for recreation. Previous research suggests that different domains of PA may have distinct effects on mental health . A seconA third limitation is the cross-sectional design of this study. The cross-sectional design does not allow us to make firm causal inferences on the associations we identified. It is possible that subjects with higher cognitive functions, more mature coping strategies, and better mental health may be more likely to engage in MVPA. Furthermore, our sample was primarily university students, which does not allow us to generalize our findings to older people or people from other settings. Future research should investigate whether our findings hold in a prospective context and other settings and whether interventions with as few as 1~2 days of MVPA cause meaningful cognitive and mental health changes.In a sample of young adults, more frequent vigorous- and moderate-intensity PA rather than walking (considered low to moderate intensity) was associated with better cognitive and mental health measures. Meanwhile, compared with no MVPA at all, as few as 1~2 days per week (lasting at least 10 minutes each time) of MVPA was associated with a variety of benefits related particularly to coping with challenging situations. In light of the neurobiological literature, the present study speaks to the value of moderate- to vigorous- rather than low-intensity PA in enhancing cognitive functions and mental health.


The transverse relaxation time (T2) of water molecules differ between tissues. Because the molecular motion of water is significantly affected by macro molecules, tissue containing fibrous polymers such as collagen has shorter T2 values. Patients with Duchenne Muscular Dystrophy (DMD) develop myocardial fibrosis in the late stage of the disease. The goal of this study was to determine the association of myocardial T2 distribution to the severity of DMD.1 = 6 ms, TE2 = 34 ms) DMD patients were grouped according to the ejection fraction (EF) and the circumferential strain (εcc) as: A: EF ≥ 56%, εcc ≥ 12%, mean age = 10.5 yrs, B: EF ≥ 56%, εcc ≤ 12%, mean age = 17.5 yrs, C: EF ≤ 56%, mean age = 17.5 yrs. T2 values were plotted for each subject as a histogram. The normalized mean histograms from each group were compared by the Full Width of Half Maximum (FWHM).Twenty six DMD patients and eight normal subjects were studied. T2 maps of the left ventricle were generated using a black blood dual spin echo method.  higher in group B (0.42 ± 0.06) compared to Group A (0.54 ± 0.08). Regression analysis show moderate association between FWHM/T2mean and |Ecc| in group A and B. (Pearson correlation coefficient r = .51).The distribution of T2 in the LV of the DMD subjects were remarkably heterogeneous compared to that of normal subjects. These characteristics may suggest early signs of diffused collagen accumulation in the LV in DMD.


Exacerbations of chronic heart failure (HF) with the necessity for hospitalisation impact hospital resources significantly. Despite all of the achievements in medical management and non-pharmacological therapy that improve the outcome in HF, new strategies are needed to prevent HF-related hospitalisations by keeping stable HF patients out of the hospital and focusing resources on unstable HF patients. Remote monitoring of these patients could provide the physicians with an additional tool to intervene adequately and promptly. Results of telemonitoring to date are inconsistent, especially those of telemonitoring with traditional non-haemodynamic parameters. Recently, the CardioMEMS device , an implantable haemodynamic remote monitoring sensor, has shown promising results in preventing HF-related hospitalisations in chronic HF patients hospitalised in the previous year and in New York Heart Association functional class III in the United States. This review provides an overview of the available evidence on remote monitoring in chronic HF patients and future perspectives for the efficacy and cost-effectiveness of these strategies. The management of patients with chronic heart failure (HF) places a high burden on health care resources due to the frequent follow-up visits combined with recurrent hospitalisations due to cardiac decompensation . Early dOver the last few decades, several studies have investigated the use of non-haemodynamic remote monitoring. However, the results have been largely inconsistent. A recently updated Cochrane review included 41 randomised controlled trials (RCTs) investigating the use of structured telephone support  or non-invasive telemonitoring  compared with standard HF care [Multiple large multi-centre prospective clinical studies and RCTs have investigated multiple non-invasive remote monitoring strategies, ranging from symptom and body weight monitoring to complex and intensive strategies including body weight, blood pressure, electrocardiography and peripheral capillary oxygen saturation. The landmark studies of high quality design and well specified intervention show no consistent beneficial effect of non-haemodynamic remote monitoring in HF patients (Tab. Multiple studies have investigated the remote monitoring abilities of implantable cardioverter defibrillator/cardiac resynchronisation therapy (ICD/CRT) devices in chronic HF patients to improve HF-related hospitalisation rates Tab. . The MOROther patient outcomes have been investigated as well, with mixed results. The IN-TIME RCT showed that using the remote monitoring abilities of the ICD and CRT devices leads to a reduction of a combined endpoint of all-cause death, overnight HF-related hospitalisation, change in New York Heart Association (NYHA) class, and change in patient global self-assessment . HoweverThe MultiSENSE algorithm aims to predict the individualised risk for worsening of HF based on first and third heart sounds, thoracic impedance, respiration rate, the ratio of respiration rate to tidal volume, heart rate and patient activity. This could aid in the timely detection of HF worsening with the threshold retrospectively calculated by the algorithm. However, the overall sensitivity is only 70% . AnotherIn HF patients cardiac filling pressures rise weeks before an exacerbation of HF leading to a related hospitalisation. Symptoms of clinical congestion such as gain in body weight will occur about 2 weeks later, usually shortly before hospitalisation  can be directly measured using a LAP device. The tip of this device is implanted transvenously into the atrial septum oriented towards the left atrium, enabling remote LAP monitoring. This device was used only in the LAPTOP-HF trial, which aimed to investigate the safety and effectiveness of this sensor. However, the enrollment was stopped early due to a perceived excess of procedure-related complications. This is an important issue as the procedure needs an interatrial septum puncture and is placed in the left side of the heart with the risk of arterial side complications. However, in the patients already included in this trial, and followed for 12 months, a 41% reduction of HF-related hospitalisations was observed in the patients with a LAP device . CurrentOff all the remote monitoring strategies currently available, remote haemodynamic monitoring using the CardioMEMS HF system device  Fig.  appears The CardioMEMS consists of a coil combined with a pressure-sensitive capacitor sealed in a capsule, forming an electrical circuit that resonates at a specific frequency when it is electromagnetically coupled with an external antenna . This anr2 = 0.90 at implantation and r2 = 0.94 at follow-up, p < 0.01) [r2 = 0.80 at implantation and r2 = 0.75, both p < 0.01 at follow-up) was found between PAP measurements by the CardioMEMS and estimated pressure measurements by echocardiography [Two studies have validated the PAP measured by the CardioMEMS, with cardiac filling pressures measured by Swan-Ganz catheterisation or echocardiography directly after implantation and after 6 months of follow-up , 30. Swaiography .n = 8) of patients developed a device-related adverse event, and 1% (n = 7) developed a procedure-related adverse event. The following events were reported: four bleeding events, three anticoagulation-related hospitalisations, two pre-existing atrial dysrhythmia exacerbations during implantation, two febrile illnesses, one pulmonary in situ thrombus during implantation that was treated with anticoagulation, one cardiogenic shock, one case of atypical chest pain, and one delivery-system failure requiring a snare to remove the delivery system [n = 35) or access-site-related bleeding (n = 15). The reported adverse event rates are comparable with those of a standard right heart catheterisation, which is considered a safe procedure [The safety of the CardioMEMS has been investigated in the CHAMPION trial. A total of 15 serious adverse events occurred during all implantation attempts in the CHAMPION trial . In totay system . An analy system . Most adrocedure . The recThe CardioMEMS was investigated for the first time in the CHAMPION trial . In thisp = 0.06) [The effectiveness of the CardioMEMS in preventing HF-related hospitalisations has been investigated in multiple studies , 38, 39;8, 39;3.  = 0.06) .Fig. 3CuThe recently presented PAS results confirm the consistent treatment benefit with CardioMEMS in chronic HF patients, reducing the number of HF hospitalisations in a more contemporary setting. The PAS study showed a 58% reduction in HF-related hospitalisation in the first year after CardioMEMS implantation compared with 1 year before implantation. Furthermore, a reduction in HF hospitalisations, mortality and all-cause mortality was observed after CardioMEMS implantation. However, patients included in the PAS study were their own historical controls and there has been no randomised comparison to standard care without PA monitoring.In a real-world setting, remote monitoring using the CardioMEMS leads to a similar reduction in mean PAP in both HFrEF and HFpEF patients . InteresRecently two large HF registries have been published, the CHAMP-HF registry  from theThe cost-effectiveness of remote monitoring using the CardioMEMS is highly relevant. Using the US CHAMPION trial data the incremental cost-effective ratio  for the US setting has been calculated , 48–50. There are no patient-level data for cost-effectiveness analyses in Western Europe. With assumptions and estimations based on extrapolating data from the CHAMPION trial and despite the large differences in standard care and financial systems, Cowie et al.  calculatTwo studies investigated the potential reduction of health care utilisation achieved by using the CardioMEMS , 52. In As shown above, remote monitoring of PAP with the CardioMEMS in chronic HF patients leads to more medication changes and a larger reduction of PAP compared with patients receiving standard care, indicating that these patients receive more individualised HF care. In the US, this strategy was effective in reducing the number of HF-related and all-cause hospitalisations. It was suggested that this strategy could improve mortality rates and has been shown to be cost-effective. However, as discussed earlier, some important differences in HF care exist between the USA and Europe.The 2016 ESC guidelines report on the lack of consistent evidence for non-haemodynamic telemonitoring or remote monitoring in HF patients. The guidelines state that remote monitoring may be considered in selected patients to improve HF outcome with individual approaches such as CardioMEMS to reduce the risk of HF admissions and multi-parameter monitoring with ICD (in-time approach) to improve outcome in HFrEF patients with a level IIb class B recommendation .In recent years, many remote monitoring strategies have been developed, and development continues at a rapid rate. Non-invasive remote monitoring of symptoms and signs, as well as weight, has not been proven to be effective in improving outcome measurements. Also, the monitoring of biomarkers or thoracic impedance has not been shown to be beneficial. Invasive or haemodynamic measures of remote monitoring are developed with right-sided (CardioMEMS) and left-sided (LA devices) sensors. The LAPTOP-HF trial with LA devices was stopped early for safety reasons. The CardioMEMS is the most promising (invasive) remote monitoring tool currently available. The haemodynamic information allows for a window of timely and adequate intervention based upon raised PAP, preventing an upcoming HF decompensation. Additionally, its safety and durability have been tested and confirmed in post-marketing studies. However, important information on the effect on the quality of life and cost-effectiveness is still lacking in a Western European setting, which is currently being investigated in the MONITOR-HF study.


Takotsubo cardiomyopathy otherwise called stress cardiomyopathy, which results in debilitating of a segment of heart muscles, is a sort of non-ischemic cardiomyopathy, set off by stress. We describe two case reports of takotsubo cardiomyopathy triggered by the significant stressful event being the death of pet cats. The rare nature of the type of stressor and the manifestation is something to be considered by healthcare providers. Takotsubo cardiomyopathy, also known as stress cardiomyopathy or apical ballooning syndrome, is considered a localized cardiac systolic dysfunction of the left ventricular apex and mid ventricle . TakotsuCase 1A 56-year-old male patient with insignificant past medical history presented to the ED with acute onset of severe chest pain radiating to his shoulders, started while doing work. His chest pain was associated with diaphoresis, nausea, and mild dyspnea. He stated that he was under stress because of the loss of his cat a few days prior.On examination, his blood pressure was 158/92 mmHg, his heart rate was 60 beats per minute, and his jugular venous pressure was elevated. The point of maximal impulse was situated outside the midclavicular line, S1 and S2 were within normal limits without any murmurs or gallops, and his lungs were clear. Serial ECG was performed on arrival, which showed ST-elevation in lead v4, v5, v6, and diagnosis of acute myocardial infarction was made based on EKG findings  of 25%-29% and apical ballooning. Cardiac catheterization showed no coronary artery stenosis, along with a severely reduced LVEF, which was consistent with takotsubo cardiomyopathy , the patient was discharged on supportive therapy after 15 days of hospitalization. She was continually followed up as an outpatient. After three-month follow-up, echocardiography revealed normal wall motion with an increased ejection fraction of 60%-65%. Transient takotsubo cardiomyopathy has been increasingly recognized since it was first described in Japan in 1990, and it thought to occur in 1.2% of patients with troponin-positive acute coronary syndrome (ACS) . AlthougClinically, patients with takotsubo cardiomyopathy are similar to patients with ST-segment elevation myocardial infarction, but with the absence of obstructive lesions in coronary angiography . The aboAlthough the base of the heart has an increased concentration of norepinephrine and a higher sympathetic nerve density compared to the apex, some studies suggest that the response to sympathetic stimulation from the apical myocardium can be greater; thus, the base of the heart may be more susceptible to abrupt catecholamine surges ,14.Takotsubo cardiomyopathy is normally a short-lived condition that can be treated with conservative therapy. Furthermore, decreasing physical or emotional trauma and supportive treatment can help with the quick resolution of symptoms. However, aggressive therapy is required in approximately 10% of patients who progress to acute complications such as shock and acute heart failure . In patiIn the study by Sharkey et al. , the meaTakotsubo cardiomyopathy is caused by various everyday life stressors, including, in rare cases, the death of a pet. This association should be kept in mind when dealing with cases of takotsubo cardiomyopathy to assist with early diagnosis and proper management.


Myocardial fibrosis occurs in end-stage heart failure secondary to mitral regurgitation (MR), but it is not known whether this is present before onset of symptoms or myocardial dysfunction. This study aimed to characterise myocardial fibrosis in chronic severe primary MR on histology, compare this to tissue characterisation on cardiovascular magnetic resonance (CMR) imaging, and investigate associations with symptoms, left ventricular (LV) function, and exercise capacity.mean) compared to autopsy controls without cardiac pathology.Patients with class I or IIa indications for surgery underwent CMR and cardiopulmonary exercise testing. LV biopsies were taken at surgery and the extent of fibrosis was quantified on histology using collagen volume fraction , but severity of fibrosis was not significantly higher in NYHA II-III symptomatic MR (CVFmean 15.7% [9.9–23.1] (P = 0.083). Fibrosis was patchy across biopsy sites . No significant relationships were identified between CVFmean and CMR tissue characterisation  or measures of LV function . Although the range of ECV was small (27.3 ± 3.2%), ECV correlated with multiple measures of LV function , as well as NTproBNP  and exercise capacity .120 consecutive patients  were recruited; 105 patients underwent MV repair while 15 chose conservative management. LV biopsies were obtained in 86 patients . MR patients had more fibrosis compared to 8 autopsy controls ; this difference persisted in the asymptomatic patients (CVFPatients with chronic primary MR have increased fibrosis before the onset of symptoms. Due to the patchy nature of fibrosis, CMR derived ECV may be a better marker of global myocardial status.Clinical trial registration Mitral FINDER study; Clinical Trials NCT02355418, Registered 4 February 2015, https://clinicaltrials.gov/ct2/show/NCT02355418 Chronic primary mitral regurgitation (MR) exposes the left ventricle (LV) to a volume overload, with progressive remodelling, left ventricular (LV) dilatation, and myocardial dysfunction. Despite long-standing guidelines on the indications for surgery in symptomatic and asymptomatic severe chronic primary MR, one fifth of patients continue to present post-operatively with reduced LV ejection fraction (LVEF) and an increased risk of later heart failure . AlthougEarly autopsy studies in patients with chronic severe primary MR demonstrated a stepwise increase in myocardial fibre hypertrophy and interstitial space with increasing symptoms and LV dysfunction . HoweverAll patients were enrolled in the prospective multicentre Mitral FINDER study from three tertiary cardiothoracic centres with high volume mitral valve repair programmes  between August 2015 and March 2018. Full study inclusion and exclusion criteria have been reported . In brieAll patients underwent clinical assessment with history and examination, blood sampling , symptom assessment with New York Heart Association (NYHA) classification and multiparametric CMR at the primary study site .Classification into fibroelastic deficiency (FED) versus Barlow’s disease was based on independent review of echocardiographic and CMR imaging by two experienced imaging cardiologists , and confirmed on surgery.The study received favourable ethical review from the UK National Research Ethics Service (15/EM/0243) and conformed to the Helsinki Declaration. Subjects gave written consent to participate.mean represents the mean average of CVF values from the three biopsies originating from an individual patient, and CVFmax represents the highest CVF across the three sites for the individual patient, or from all available sites in those where it was not possible to collect all three biopsies.During mitral valve surgery, three LV biopsies were obtained from each patient from the LV septum, anterior and posterior free wall, using a 14G TruCut needle or scalpel. Histological analyses were performed blinded to clinical and imaging data . Myocardial connective tissue was analysed on ×20 scanned Masson Trichrome sections  which stains extracellular connective tissue blue and stains muscle purple-red. Fibrosis burden quantified as collagen volume fraction (CVF) was derived from Ilastik machine-learning based, supervised object classification and segmentation software , which wControl myocardial samples from single whole-heart autopsy sections were obtained from autopsies of eight subjects . These data allowed comparison of age-related histological changes in subjects who died of non-cardiac causes with no evidence of macroscopic or microscopic cardiac lesions.Measurement of cardiomyocyte hypertrophy was performed by manually quantifying the cross-sectional area (CSA) of 50 randomly selected cardiomyocytes via ZEN software (Carl Zeiss Microscopy). To ensure consistency, only cardiomyocytes found in its mid-axial orientation  were eligible for quantification.LV and right ventricular (RV) volumes and mass, and left atrial volumes were acquired in line with 1.5T CMR scanner  protocols , 14. Sin®  by an operator (BL) blinded to all demographic and descriptive data, and without information regarding any clinical parameters. For ventricular volume analysis, the endocardial border was detected with thresholding, delineation of atria/ventricles was confirmed in matched long axis planes, and papillary muscles and trabeculations were included in ventricular mass. For T1 mapping, two short axis maps (base and mid LV) were manually contoured for endo- and epicardial borders. Partial voluming of blood was minimised by using a 20% offset from the endo- and epicardial border  and CVFmax of 22.2% [10.2–31.8], which were significantly higher than control CVF values . The difference in fibrosis persisted when limited to asymptomatic MR patients compared to controls . Although there was a trend towards increased fibrosis in symptomatic patients compared to asymptomatic MR patients based on NYHA classification, this was not significant (CVFmean 15.7% [9.9–23.1] (P = 0.083) .MR patients had a median CVFA total of 124 myocardial biopsies contained endocardium (median thickness 100 µm [58–181]), and 111 biospies contained only myocardium. Biopsies with endocardium showed higher CVF than those without endocardium . There was a significant correlation between mean endocardial thickness and CVF , consistent with endocardial thickening and subendocardial scar. The pattern of fibrosis varied between MR patients and within the myocardium, including diffuse interstitial fibrosis, perivascular fibrosis and areas of replacement fibrosis  for fibrosis across the three biopsy sites .2 vs 124 ± 26 µm2, P < 0.001, Fig. 2 vs 891 ± 232 µm2, P = 0.069).Direct histological quantification of cardiomyocyte hypertrophy was performed via haematoxylin and eosin (H&E) stained slides. MR patients were found to possess marked cardiomyocyte hypertrophy compared to controls , there were no signficiant correlations with CMR parameters, including native T1 or ECV. There was however, a near-significant correlation with age .During examination of surgical biopsies, fat infiltration between cardiomyocytes was noted. As a potential confounder to T1 and ECV measurements (T2 mapping was not performed), fat infiltration was semi-quantitatively assessed by an experienced cardiac histopathologist blinded to clinical and imaging data using a scale of 0 (no fat infiltration) to 3 (prominent fat infiltration). Of 79 biopsies assessed, 52 (66%) contained no fat infiltration, 15 (19%) mild; 10 (13%) moderate; and 2 (3%) prominent fat infiltration , or ECV  regardless of whether analyses were performed according to global values .The extent of histological fibrosis quantified on biopsy by CVFues Fig. a or accomean was not significantly correlated with the amount of left ventricular LGE .LGE was present in 34 (33%) of 102 patients who received gadolinium-based contrast agent, with a median mass of 0.98 g (IQR 0.33–2.47). Mid-myocardial LGE was located in the basal inferolateral LV segment (n = 23), and/or in the papillary muscles (n = 8), basal anterolateral segment (n = 3), mid inferolateral segment (n = 2) and mid septum (n = 1). The extent of histological fibrosis quantified on biopsy by CVFmean was not significantly correlated with CMR measured LV volumes, LVEF or LV mass, and there was no relationship with other imaging markers of LV function, including GLS and E/eʹ. There was however, a signficant positive correlation between CVFmean and NTproBNP  . There was a consistent and significant correlation however, between ECV and multiple parameters of LV function  and E/eʹ), as well as NTproBNP. The amount of LGE in the cohort was small and there was no significant difference in CMR measured LVEF, LVESVI or GLS, E/eʹ or NTproBNP between patients with or without LGE.The extent of histological fibrosis quantified on biopsy by CVF1) Table . Sub-ana2) was 23.2 ± 7.4 ml/kg/min, giving a %PredVO2max of 92.9 ± 20.5%, at an age-predicted heart rate of 99.0 ± 14.8%. On linear regression, formally tested exercise capacity quantified as %PredVO2 max was significantly associated with ECV, markers of biventricular systolic function, E/eʹ, the presence of atrial fibrillation, and pulmonary artery systolic pressure, but not with CVFmean (Table Four patients undergoing surgery were unable to complete cardiorespiratory symptom-limited CPET due to non-cardiorespiratory causes (severe osteoarthritis and anxiety). Mean peak oxygen consumption , but not CVFmean . There were no significant differences in biventricular volumes, LVEF, LVMI or MR severity; ECV and LGE prevalence were also similar  or MR severity. Biopsy and CMR offered complementary information however, because patterns of fibrosis proved variable, and CMR-derived ECV and LGE were not able to capture the subendocardial changes highlighted on histology. Hence, while the extent of fibrosis on myocardial biopsy was related to symptoms but was not related to LV function, non-invasive tissue characterisation with ECV was associated with changes in both systolic and diastolic function, and measured exercise capacity.The new finding of significant myocardial fibrosis in asymptomatic patients contrasts with early autopsy data, which found a significant increase in the size of the interstitial space only in those patients with severe MR (NYHA Class III–IV) who died early after mitral valve replacement from cardiac failure with low cardiac output syndrome . Althougmean and CMR measures of fibrosis. There are a number of potential reasons for this. Similar to previous reports [Despite evidence that high native T1, elevated ECV, and LGE measure diffuse interstitial and replacement fibrosis in other diseases –24, we f reports , we note reports , and mir reports . We repo reports . This maThis study was observational in nature and therefore no causation can be inferred. Although pre-specified, invasive myocardial biopsy was not performed in all patients with symptomatic and asymptomatic MR who went forward to surgery due to technical difficulties. Despite this, we provide the largest histologic characterisation of patients with severe primary MR. We were unable to anatomically match the location of the autopsy sections with the location of our histological biopsies. However, there is no evidence for significant regional variations in CVF quantity in the healthy heart and therefore this limitation should not detract from the significant difference in CVF observed between MR patients and controls. Similarly, anatomical matching of the location of biopsy collection with the commonly observed location LGE in MR is difficult, and is likely to contribute towards the lack of association between CVF and LGE quantification. Invasive measurement of pulmonary artery pressures was performed at the clinician’s discretion and was not a requirement of this study. Although assessment by echocardiography was performed, there were cases inevitably without enough tricuspid regurgitation for pulmonary artery systolic pressure to be measured. Finally, the narrower range of global fibrosis quantified by ECV may have weakened our ability to detect correlations, where a broader range always favours the likelihood of obtaining significant results. However, studying a group of severe MR patients early in their disease process increases the clinical relevance of our findings given the trend for earlier surgical assessment of asymptomatic patients.Histological evidence of diffuse interstitial and replacement myocardial fibrosis, along with concomitant cardiomyocyte hypertrophy is present in asymptomatic MR, in the presence of normal range LV volume and LVEF. Fibrosis on biopsy is patchy and highly variable within the heart, which may contribute to the lack of correlation with T1 mapping, ECV and LGE. ECV, as a marker of global myocardial status, correlated well with multiple measures of ventricular function in MR. Further studies are warranted to investigate whether latent fibrosis detected using T1, ECV or LGE offer incremental value in predicting post-operative outcome in asymptomatic patients with severe primary MR.Additional file 1: Table S1. Clinical characteristics of conservative and surgical patients. Table S2. Cardiac magnetic resonance parameters according to subtype of MR. Table S3. CVFmean values according to symptom status and biopsy type.Additional file 2: Figure S1. Scatter plots demonstrating the correlation between regional ECV and CVF in the A) septum , B) anterior wall  and C) posterior wall  of the left ventricle.