MitraClip edge-to-edge (E2E) repair system is the only transcatheter device recommended in the current guidelines for treating mitral regurgitation (MR). The percutaneous femoral venous transseptal access of MitraClip requires a complex steerable delivery system and may thus be technically complex to optimally position and deploy the clip onto the mitral valve. A transapical approach for E2E repair has been devised to treat MR for the ease of operation . The first-in-human study of ValveClamp has demonstrated its early feasibility and effectiveness for the treatment of patients with degenerative MR. Transesophageal echocardiography (TEE) is the only imaging modality required for intraoperative guidance of ValveClamp implantation. Successful implantation depends on accurate localization and orientation of the clamp and efficient intraoperative communication between the echocardiographer and the intervention team. Thus, the focus of this review is on elaborating how two-dimensional (2D) and three-dimensional (3D) TEE are used in clinical practice to guide ValveClamp implantation and it may facilitate the understanding of simplicity and safety of this novel procedure. We also describe the implementation of several novel advancements in 3D TEE imaging, which improve the confidence of image interpretation for intraoperative guidance and expedite implantation times. Transcatheter mitral valve (MV) interventions are progressively being introduced into clinical practice targeting a population of patients with mitral regurgitation (MR) deemed inoperable or at a prohibitive surgical risk . EchocarThe MitraClip edge-to-edge (E2E) repair system is the only transcatheter device recommended in the current guidelines for treating MR.  The percRecently, a transapical approach for E2E repair has been introduced to treat MR for the ease of operation . The first-in-human study of ValveClamp has demonstrated its early feasibility and effectiveness for the treatment of patients with degenerative MR (dMR)  and poteTransesophageal echocardiography (TEE) is the only imaging modality required for intraoperative guidance of ValveClamp implantation. Successful implantation depends on accurate localization and orientation of the clamp and efficient intraoperative communication between the echocardiographer and the intervention team.Transapical E2E repair using ValveClamp has its own distinct characteristics on echocardiographic imaging for intraoperative guidance. While assessment of mechanism and grading of MR, as well as the procedural effect after transcatheter E2E repair, has been well established –14, thisTransapical E2E repair using ValveClamp system involves the introduction of a user-friendly leaflet clamp into the left atrium (LA) and coaxial deployment of the clamp to the mitral valve , which cTransseptal puncture, as well as fluoroscopy guidance, is omitted during the procedure. For percutaneous femoral venous transseptal access repair devices, such as MitraClip and PASCAL, fluoroscopy may provide additional helpful information in regard to the opening, orientation, and adjustment of the device. During ValveClamp implantation, the accurate localization and orientation of the clamp thus completely rely on the intraoperative real-time 2D and 3D TEE imaging.The key to a successful procedure using ValveClamp is explicit mutual communication between the echocardiographer and interventionist. A real-time display is needed for both sides to view the echocardiographic images.Recent advancement in TEE  provides increased resolution and tissue filling in 2D and real-time 3D visualization and meanwhile enables one-beat acquisitions with high volume rates in real-time 3D and 3D color flow Doppler (CFD) imaging. Photo-realistic 3D rendering techniques  are designed to improve visualization of anatomical structures that appear pink-to-red depending on the intracardiac position of a virtual light source , 16.These novel imaging techniques are now routinely used at our center for guidance in transapical E2E repair procedures and this protocol described in this review article is primarily based on the implementation of these techniques.Localization of the cardiac apexThe ValveClamp implantation procedure is performed in the hybrid operating room with patients under general anesthesia. TTE apical 4-chamber view is used to locate the cardiac apex. To obtain this view, the transducer is usually positioned at the left fifth or sixth intercostal anterolateral space. Ideally, it encompasses a full view of all four chambers, including full visualization of the LV to avoid foreshortening. A marker is then made at the site of the probe. After confirmation of the location, a left anterolateral minithoracotomy is performed to expose the apex. In situations that the apex lay under the sixth costa, incision can be made at the fifth intercostal space and the surgeons would use infilling outside the diaphragmatic surface of the heart to facilitate exposure.Transapical punctureTo identify an appropriate puncture site, the interventional cardiologist can gently press the apex by fingertip. In detail, the notch of the fingertip is expected to be simultaneously displayed on the apical site of X-plane views and oriented toward the center of the MV orifice . The punA double pledget-supported purse-string suture is made around the predetermined puncture site prior to introducing the puncture needle and guidewire into LV. Then, the guidewire is advanced into LV and LA at the diastolic phase under X-plane view and adjusted laterally/medially or anteriorly/posteriorly to the center of MV orifice. It will be easily identified on X-plane view and 3D enface LA MV view .A 6F guidewire is then exchanged and advanced into LV and LA. A similar view is used to visualize and adjust the guidewire to the center of the MV orifice, so as to further confirm the accuracy of the puncture site .The 16F introducer sheath is then inserted into LV via the 6F guidewire. Under X-plane view and 3D enface LA MV view guidance, the introducer sheath is slowly advanced into papillary muscle level. In general, the insertion depth is approximately 3 cm .Introducing the valve-crossing deviceThe next step is to withdraw the 6F guidewire and load the valve-crossing device into the introducer sheath.The valve-crossing device comprises a cylinder mesh made of a nitinol alloy and a stainless-steel rod. The cylinder mesh can produce elastic deformation when contacting with cardiac tissue, such as MV leaflet, chordae tendineae, and LA wall.In order to exclude the interference of chordae tendineae, it is essential to identify possible deformation and resistance when passing the valve-crossing device through a subvalvular structure .If necessary, the interventionalist could withdraw the valve-crossing device back to the left ventricle and repeat the valve-crossing movement. This aims to further exclude the involvement of any chordae tendineae.The following step is to advance the introducer sheath into the center of LA along the rod of the valve-crossing device while keeping the valve-crossing device steady. It is of critical importance to monitor the path of the introducer sheath inside the LA and the spatial relationship between the tip of the introducer sheath and LA wall using X-plane view or 3D enface LA MV view + X-plane view . A recomAdvancement and adjustment of the clampThe clamp is inserted into the introducer sheath and sent to the left atrium under X-plane view or 3D enface LA MV view + X-plane view monitoring. The clamp proceeds slowly until the opening of the proximal (front) clamp is visualized. Next, to open the rear clamp, the introducer sheath is carefully pulled back.The clamp then needs fine adjustment of (a) its position by shifting on the lateral-medial and anterior-posterior axis of the MV until it is above the target grasping area; (b) its perpendicularity to the MV orifice commissural line by rotating it clockwise or counterclockwise ; and (c)Leaflet GraspingAfter verification of its position and orientation, introducing by X-plane view or 3D enface LA MV view + X-plane view, the delivery system was withdrawn slowly so that the rear clamp was entering into the LV and the proximal clamp remained within the LA Figures . The oriAt this point, the proximal clamp is drawn back  to captuME-LAX view allows confirmation that (a) both leaflets are within the arms of the clamp and (b) the approximation of the proximal clamp has induced a full grasping of the leaflet.The configuration of the clamp arms expands the range for leaflet grasp, which is considerably larger than that of MitraClip despite their arms' similar size. This characteristic may make it easier to grasp leaflets with ValveClamp and potentially affords a greater chance of procedural success especially in patients with a large flail gap. .Valve function assessmentAssessment of the grasping effectiveness is of importance and depends entirely on 2D and 3D TEE. The assessment covers 4 aspects: length of leaflet insertion, severity of residual regurgitation, MV geometry, and degree of stenosis .Length of anterior and posterior leaflets of MV in the diastolic phase can be measured in the LAX view of X-plane view just before and after grasping, and the length of leaflet insertion can be obtained, which equals the difference between the length of leaflets before and after grasping. A minimum of 5 mm is deemed adequate for ValveClamp.This assessment of residual regurgitation usually uses multimodal criteria per the current guideline, especially in case of incomplete correction of MR.  The presIn daily practice, 2D and 3D CFD imaging allow visual detection of residual mitral jets. The grading scheme of residual MR has yet to be validated, but the jet dimension into the left atrium is routinely screened to exclude significant regurgitation. 3D CFD helps the implanting team determine whether the clamp should be adjusted or additional clamp is indicated .In central MR jets, a symmetric double-orifice MV is typically created, and the residual mitral orifices areas can be measured through direct planimetry . The graRelease of the clampIf the above four criteria are satisfied, the clamp can be released. This process must be monitored using 2D and 3D TEE. At this point, the delivery rod that holds the clamp and valve must be steady to avoid leaflet tethering.If the above four criteria are considered not satisfactory, the closed ring could be reversed to reopen the clamp. The rear clamp could be moved back to the LA during diastole and the above clamping steps then could be repeated.2, mean transmitral gradient ≤5 mmHg, and both anterior and posterior leaflet length>10 mm at the regurgitant site. Implantation of a second clamp should start with another valve-crossing manipulation. If the residual MR is deemed moderate or more after deployment, additional clamps should be considered. The following criteria should be satisfied before the next implantation in our center: mitral valve opening orifice area ≥3.5 cmIt is reported that approximately one-third of patients with dMR had noncentral dMR, highlighting the significant prevalence of noncentral MR , 22. If The X-plane angle of the initial ME-commissural view can be corrected by either subtracting 10–40° for A1/P1 pathologies or adding 10–40° for a prolapse in the A3/P3 segment. This will permit a perpendicular LAX view as the 90° angle between the biplane angles is maintained. .The design and route of the ValveClamp system permit coaxial adjustment of perpendicularity and position of the clamp within the medial and lateral MV aspects. Care should be taken during this process to circumvent contact of the clamp arms with the LA wall. Also, leaflet length at the target site should be >10 mm.Surgery represents the standard of care for dMR owing to excellent efficacy and long-term results of mitral valve repair. The current iteration of the ValveClamp system  was only used for patients with dMR with prohibitive surgical risk . A transapical E2E repair can be considered depending on the mitral valve anatomy evaluated by the interdisciplinary Heart Team.The transapical access, compared to the percutaneous approach, may bring a higher degree of myocardial injury, especially in elderly patients with reduced LV ejection fraction preprocedurally, and harmful effects of thoracotomy according to the transcatheter aortic valve replacement literature , 24. HowThis review describes a systematic and easy-to-perform 2D and 3D TEE guidance protocol for transapical E2E repair. This protocol has several advantages compared to that of other transcatheter mitral valve repair devices: (1) this protocol entails only a few standard 2D and 3D views recommended by the current guideline, which would provide a steeper learning curve for echocardiographer and interventionalist and simplify the implantation steps; (2) it highlights the combination use of real-time 2D and 3D TEE imaging, instead of frequent probe manipulations and transpositions with 2D TEE, to consistently and precisely monitor and guide the procedure; (3) TrueVue real-time 3D imaging technique makes it simpler to visualize the spatial relationships between the delivery system and clamp, and the interventional objective and adjacent vital structures by providing images with tissue detail and depth perception, improving the confidence of image interpretation.


Left ventricular (LV) structure and function anomalies are frequent during the CKD continuum and are associated with increased risk of mortality. Cross section and longitudinal ultrasound data are available for advanced CKD and transition to ESKD. Less information is available about LV changes during stable, long-term hemodialysis (HD) treatment. All stable HD patients from 9 HD centers  have been enrolled in January 2015. The cohort was followed-up for 4 years, kidney transplantation or death. Yearly, two-dimensional and M-mode continuous and Pulse Doppler echocardiography were performed. During the follow-up, the prevalence of cardiovascular comorbidities significantly increased (p < 0.0001), coronary artery disease (CAD) from 73.5 to 88.8%, peripheral artery disease (PAD) from 29 to 40.9%, cerebral vascular disease (CVD) from 20.4 to 30.8%, heart valves calcification (VC) from 65.6 to 89.3% and left ventricular hypertrophy (LVH) from 67.6 to 76.5%. The mortality risk increased with the presence of CAD (1.59-fold), PAD (1.61-fold), CVD (1.59-fold), and VC (1.77-fold). Mortality risk was increased in those with LVEF < 50% (LVEF 40–49% 1.5-fold and LVEF < 40% 2.3 fold). Among the survivors of the first year, LVEF varied . More than 5% increase of LVEF was associated with higher mortality risk  compared to stationary EF (p = 0.001). Cardiovascular disease progresses during stable long-term HD therapy and increases mortality risk. HF becomes highly prevalent but only HF with decreased LVEF < 50% is associated with increased risk of mortality. Therefore, in end stage renal disease (ESRD), cardiovascular comorbidities are common  even in young patients2. In these patients, CVD remains the main cause of death. The renal registries  and cohort studies (2014 Swedish cohort) reported a CVD related mortality varying between 27 and 69%4.The mortality of hemodialysis (HD) treated ESRD patients is very high compared to the general population (in Europe 8.8-fold higher for CVD and 8.1-fold higher for non-cardiovascular causes)7. Most of the available data are based on cross-sectional design studies or post hoc analysis of trial participants. The longitudinal study of a subset of CRIC participants exploring left ventricular structure and function at transition from advanced CKD to HD (2013)8 and the Japanese observational cohort study from 2013, exploring longitudinal evolution of vascular and heart valve calcifications in HD patients9 are among the few exceptions.In advanced CKD and ESRD, left ventricular structure and function anomalies  investigated by a large variety of imaging methods, proved to be associated with high cardiovascular and all-cause mortality riskLess is known about long-term HD therapy and its effects on myocardial structure and function under the novel conditions: anemia and erythropoietin stimulating agents (ESA) therapy, chronic kidney disease–mineral bone disorder (CKD-MBD) and its treatment, fluid overload, novel blood pressure conditions, novel diet and metabolism conditions, and so on.The aim of our multicenter longitudinal observational cohort study was to continue to explore left ventricular function and structure changes and their impact on mortality in stable HD treated ESRD patients. Also, in this study, we highlight clinical and laboratory predictors of adverse events. We describe mortality according to baseline hearth failure and also describe the impact of the changes in the value of EF on mortality.All stable HD treated ESRD patients (> 90 days HD therapy) from 9 HD centers from Romania have been enrolled in the study in January 2015. The cohort consisted of 1034 patients,  average age 58.71 ± 12.94 years. Personal data, history of disease, HD therapy parameters were retrieved from patient’s dialysis files. Diabetes mellitus (DM) was evidenced in 20.9% patients at inclusion. HD therapy was performed using high flux, high surface dialyzers, 3 times/week (≥ 12 h/week) in all cases. The assessment, therapy and follow-up of anemia and CKD-MBD were performed according to KDIGO guidelines. The cohort was followed-up for 4 years or kidney transplantation or death. The study was approved by the Ethics Committee, of the Avitum BBraun Romania Dialysis Center, and all patients signed a written informed consent. The study was in accordance with the Ethics Code of the World Medical Association.10.Yearly, two-dimensional and M-mode continuous and Pulse Doppler echocardiography were performed in accordance with the recommendations of the European Association of Cardiovascular Imaging (EACI), between the 2nd and 3rd hour of dialysis session, by the same operator using the same device (in order to avoid inter-observer differences). After a regular exam of cardiac morphology and function, we assessed the left ventricular ejection fraction (LVEF) by using the Simpson method, and we noted the presence of heart valve calcifications. Heart failure (HF) was assessed by the presence of clinical features  and with structural and/or functional anomalies of the heart according to the European Guidelines on Acute and Chronic Heart FailureNo HF (NHF): no clinical features, EF not altered.HF with preserved EF (HFpEF): presence of symptoms/signs and LVEF ≥ 50%.HF with mid-range EF (HFmrEF): presence of symptoms/signs and LVEF 40–49%.HF with reduced EF (HFrEF): presence of symptoms/signs and LVEF < 40%.According to these guidelines, patients were divided into 4 groups:13.Diagnosis of coronary artery diseases (CAD), Cerebrovascular Disease (CVD) and peripheral artery diseases (PAD) was assessed according to the guidelinesData are presented as average ± standard deviation , median and interquartile range  respectively percentage from the sub-group total and number of individuals. Continuous variables distributions were tested for normality using Shapiro–Wilk test, and for equality of variances using Levene’s test. We employed ANOVA test in order to check if age introduced a survival bias. The individual impact of several confounding factors on the variance of a continuous variable was assessed by building multivariate regression models. The quality of the model was described using the accuracy of prediction and by Nagelkerke’s R2. The predictors, in the final regression equations, were accepted according to a repeated backward-stepwise algorithm  in order to obtain the most appropriate theoretical model to fit the collected data. For assessing survival, we employed Kaplan–Meier survival curves with the Breslow test for pairwise comparison. We only right-censored at the time of kidney transplant or 1 January 2019. The end-point of this study was death. We test our data for proportional hazard assumption and since it was not violated, we continue with Cox proportional hazard regression models that were employed to estimate hazard ratio.In this study, a p-value of 0.05 was considered the threshold for statistical significance. Data were analyzed using SPSS v26 statistical software package  for Linux.The baseline characteristics of the investigated cohort are presented in Table The prevalence of the main comorbidities has been assessed yearly. At the end of the study, all cardiovascular comorbidities were significantly more prevalent compared to inclusion (p < 0.0001): CAD—88.8% vs 73.5%, PAD—40.9% vs 29%, CVD—30.8% vs 20.4%, Vascular/heart valve calcification (VC) 89.3% vs 65.6%, Left ventricular hypertrophy (LVH) 76.5 vs 67.6%. During the 4-year follow-up time, all-cause mortality was 25.3% (261 patients died). The survival rate in the first year was 90.5% (98 deaths), in the second it was 85.9% (48 deaths), in the third it was 77.3% (59 deaths) and in the fourth 74.7% (56 deaths).2 = 0.286). The risk of death increases with the presence of CAD (by 1.59-fold), of PAD (by 1.61-fold), of CVD (by 1.59-fold) and VC (by 1.77-fold). Increased eKt/V, higher ejection fraction and dry weight turned out to decrease the risk of mortality , along with the laboratory and the echocardiographic results. Akaike information criteria (AIC) was used in order to determine the best model. Odds ratio and 95% confidence interval were calculated. Our regression equation proved to be a good fit for the model, explaining 28.6% of death event . ANOVA test shown no statistically difference of survival between age groups (p = 0.204). Also, the female group in this study was not under represented, similar incidence of male/female ratio is present in European populationThe patients from our cohort were assigned to the four HF groups as described in methods: NHF n = 612), HFpEF (n = 266), HFmrEF (n = 118) and HFrEF (n = 38). Kaplan-Meier survival analysis was conducted to compare the four groups  = 17.963, p < 0.001). Pairwise comparisons were conducted to determine which group had different survival distribution and the results are presented in Table A Breslow test was conducted to determine if there were differences in the survival distribution in the four groups. The survival distribution for the four groups were statistically different, , in the second EF decreased more than 5% (n = 262), and the third EF increased more than 5% (n = 250). EF trend analysis included patients who survived at least one year in order to get a second ultrasound investigation (n = 936). We observed that the group where EF increased more than 5% had a higher number of events, with a 76.4% survival rate compared with the ± 5% group (85.8%) and the > 5% EF decrease group (83.2%). , increased left ventricular mass index (LVMI), diastolic dysfunction, decreased left ventricular ejection fraction (LVEF) are common in pre dialysis CKD patients and associated with poor cardiovascular outcome17. In CKD patients, even with normal LVEF, early detection of impaired LV myocardial function was possible by two and three-dimensional speckle-tracking echocardiography and was associated with higher CV risk18. The high mortality rate in advanced CKD and ESKD was related to LV dyssynchrony also19. Myocardial structure and function anomalies progress along the CKD continuum related to hypertension, fluid overload, anemia, uremic toxins, myocardial fibrosis, coronary artery disease (CAD)and so on20.Since 2003 (JNC 7) CKD is considered a major risk factor for CVD. As CKD progresses, the prevalence of conventional CVD risk factors increases and novel (CKD related) risk factors emerge21. All those changes are influencing myocardial function and structure and may change ultrasound findings also. Indeed, initiation of HD induced decrease of LVMI, concentric or eccentric remodeling of LVH in heart failure HD patients22. In preserved LVEF patients, 2D strain analysis showed a better left ventricular function in HD patients as compared to advanced CKD ones23. Based on these findings, early initiation HD was proposed. The Echo sub study of the IDEAL trial failed to evidence any heart ultrasound traceable benefits in the early initiated patients compared to the late initiated ones (GFR 10–14 vs 5–7 mL/min/1.73 m2)24. The meta-analysis of 46 small studies concerning the effects of more intensive HD therapy  showed improvement of myocardial function and morphology in the intensive group. No cardiovascular survival benefits were explored in the study25.Initiation of hemodialysis (HD) in ESKD seems to change some of these risk factors by reducing blood pressure, eliminating some of the uremic toxins, better controlling the fluid overload, acid–base and electrolyte balance. At the same time some other risk factors emerge, excess of endotoxins, consequences of the AV fistula, myocardial stunning, HD induced hemodynamic stress8.The first study following up the ultrasound structure and function changes from advanced CKD to ESRD (HD) was performed on a subset of patients from the CRIC . The ultrasound findings one year prior to HD initiation and one year HD therapy evidenced no significant changes in LVMI but a significant decrease of LVEF26. As recently suggested, during long term HD therapy, the cumulative effect of many novel cardiovascular risk factors , play an important role in the progression of cardiovascular disease and of cardiac structure anomalies27.According to our knowledge this multicenter longitudinal study is the first to explore changes of myocardial function and structure in a large cohort of 1034 stable HD patients (average HD vintage at inclusion 3.56 years). As expected, during the 4 year follow-up the prevalence of clinically evident CAD, PVD and CVD significantly increased . On echocardiography, these data have been associated with increasing prevalence of LVH from 67.6 to 76.5% and of heart valve calcifications from 65.6% to 89.3% . We should emphasize the very high and increasing prevalence of VC in our cohort as compared to the USRDS data (35 to 40%)28.In the four year follow-up time 261 patients died . The survival rate decreased, being 90.5%, in the first year, 85.9%, in the second, 77.3% in the third and 74.7% in the fourth. The risk of death increased with the presence of CAD by 1.59-fold, with the presence of PAD by 1.61-fold, of CVD by 1.59-fold and of VC by 1.77-fold. It seems that increased eKt/V and dry weight, higher LVEF were associated with decreased risk of mortality. Similar data have been reported in Japan in patients over 10-year treatment with HD10. The patients in the groups with LVEF > 50% had a significantly higher estimated survival as compared to those with LVEF < 50% . The mortality risk was also higher in the group 3 (1.5-fold) and 4 (2.3-fold). Reduced LVEF at starting of HD represent a strong independent predictor of cardiovascular death29. 40.8% of the patients had heart failure criteria according to 2016 ESC guidelines10. In contrast to some of the prior publications30, estimated survival was lower and risk of death were higher only in the groups with LVEF < 50%, meaning in 15.08% of the entire cohort (excluding the HFpEF group). Our results in a cohort of ESKD patients treated with HD are similar to those published by the MAGGIC group meta-analysis31.The average LVEF at inclusion was 57.69 ± 9.54% and 15.08% of the cases presented a LVEF < 50%. We assigned the patients to the groups presented in methods32. One could expect a decrease of risk with the increase of EF. On the contrary, in our cohort, the increase of EF was associated with an increase of mortality risk. We hypothesized that an increase of LVEF was induced by more or less permanent heart valve regurgitation due to fluid overload, changing pressure regimen on both sides of the valves, accelerated progression of CAD, valve calcification induced by CKD-MBD, uremic cardiomyopathy, all common in HD patients. There were no correlations between the EF trend and vascular calcifications. In these cases, maybe global longitudinal strain alteration should be used as risk marker of cardiovascular mortality, as we have already mentioned.At the second echocardiography performed 1 year after inclusion in the cohort, in the first year survivors (n = 936), we detected some variations in the LVEF. In order to assess the significance of those variations, we divided the cohort into 3 groups: a group with > 5% decrease of LVEF (n = 262), a group with less than 5% variation of LVEF (n = 424) and a group with more than 5% increase of the LVEF (n = 250). Using the group with less than 5% variation of LVEF as reference, the Cox regression analysis evidenced an increase of mortality risk 1.43-fold in the group with more than 5% increase of EF, when adjusted for age, gender and initial LVEF. In the group of patients with > 5% decrease of LVEF the mortality risk was 0.84 (not significant). LVEF is a risk stratifier for all cause and cardiovascular mortality in HF patientsChanges in ejection fraction were noticed as consequences to ischaemic condition—myocardial infarction or ischemia, and to valvular changes and so-called improvement of EF was due to volume overload in augmented regurgitated flow. We tried to assess EF in hemodynamic stable condition, in patients with normal heart rate 60–80 b/min and stable blood pressure.We want to stress the importance of EF changes during time, EF might vary consistently due to volume overload of cardiac origin in the case of valvulopathies or of dialysis origin in the overhydrated patients. Also, this parameter might vary in arrhythmias or acute conditions, so our evaluation was done in stable condition. An improvement of EF might not be always a marker of good prognosis.Cardiovascular disease progresses during stable long-term HD therapy and increases mortality risk. The novel (HD related) cardiovascular disease risk factors seems to further increase prevalence of LVH and decrease LVEF. HF becomes highly prevalent in long term HD treated patients but only HF with decreased LVEF < 50% is associated with increasing risk of mortality. More or less permanent increase in LVEF, under these conditions, being associated with increased mortality risk, may reflect a dynamic process of volume compensated increase of heart valves/contractility dysfunction.These findings support the idea of repeated echocardiographic evaluation in order to reveal as soon as possible changes in morphology with hemodynamic consequences.The cardiac evaluation was made during the dialysis sessions. The adherence of HD patients to long term follow-up studies needing repeated investigation effort is low as suggested by others. Therefore, we applied the settings suggested by other authors also. The blood pressure was not evaluated during the dialysis session due to the fact that it is highly variating during the procedure. We didn’t evaluate the valvular changes, but the changes are relatively small on the yearly evaluation.The number of patients is high and the follow-up period is significant .


To explore the evaluation of left ventricular diastolic function (LVDF) in patients with coronary heart disease (CHD) using ultrasound images (UI) combined with electrocardiogram (ECG) on bilateral filtering image noise reduction algorithm (BFINRA).A BFINRA was constructed, and 60 subjects who were investigated were divided into a control group (CG) from June 2019 to November 2019 in Taizhou People’s Hospital, a myocardial infarction group (MIG), and an angina pectoris group (APG). The patient’s LVDF was examined by two-dimensional electrophoresis (2DE) and real-time three-dimensional echocardiography (RT-3DE) combined with ECG. The results showed BFINRA could improve UI quality.Clinical data indicated there were no substantial differences in age, gender, and fasting blood glucose of all subjects. 2DE examination results showed the left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and early diastolic mitral blood flow velocity / early diastolic mitral annulus velocity (E/E’) of MIG were much higher than CG (P<0.05), while the left ventricular ejection fraction (LVEF), E / late diastolic mitral blood flow velocity (E/A) and E’ peak value were sharply decreased (P<0.05);LVESV and E/E’ of APG were increased dramatically (P<0.05), while E peak, E/A and E’ peak were decreased greatly. RT-3DE examination results indicated LVEDV and LVESV of MIG were considerably higher than CG (P<0.05), while LVEF and macrophage resistance factor (MRF) were enormously decreased (P<0.05);LVEDV and LVESV of APG were greatly increased (P<0.05). However, LVEF and MRF were not changed significantly (P>0.05). LVEDV had a remarkable difference (P<0.05), but LVESV and LVEF had no obvious differences (P>0.05). The electrocardiogram results illustrated the increase in QT dispersion (QTd) of MIG and APG was statistically significant (P<0.05) compared with CG, while the negative increase of P-wave terminal force in lead V1 (PTFV1) also had a statistical significance (P<0.05). Correlation analysis revealed that MRF and PTFV1 had positive correlation, while MRF and QTd showed a negative correlation.The combination of UI and ECG could better assess LVDF in CHD patients. RT-3DE has greatly improved the application of ultrasound diagnosis in the evaluation of cardiac morphology and function, which does not rely on geometric assumptions and can reflect the dynamic changes of the heart chamber volume in real-time to obtain the left ventricular volume-time curve (VTC).To evaluate the differences in the diagnosis of patients with coronary heart disease by electrocardiogram, two-dimensional echocardiography, and three-dimensional echocardiography, the optimized bilateral filtering algorithm was adopted to denoise the echocardiogram, and then the UI was combined with ECG to evaluate the LVDF of CHD patients. The study was intended to provide a reference for improving the diagnosis efficiency of coronary heart disease and the treatment effect of patients.Gaussian filtering was to assign different spatial position weights to pixels in the image range and obtain the pixel values of the points to be processed by the weighted average method, as shown below.h(m) represented the output value of the pixel, f(ξ) and c represented the set of input pixels and the spatial position weight, respectively;and Kd(m) represented the unitization factor to ensure that the absolute smooth position gray value remained unchanged.Here, It showed from the above that Gaussian filtering only considered the spatial position relationship among pixels, but ignored the processing of image edge information. Edge information expressed abstract information in the images, such as texture detail information and locations with greater color contrast.ξ),f(m)) and rk(m) stood for the pixel similarity weight and unitization factor, respectively. A new bilateral filter function was obtained through the combination of the pixel similarity weight and unitization factor, which not only considered the spatial position relationship, but also the degree of pixel similarity. The theoretical equations were expressed as follows.Where, s was discretized and rewritten, and the calculation of bilateral filtering limited in the neighborhood was expressed in the following.Where Ω represented the set of neighborhood pixels around the target points, and the basis for the realization of bilateral filtering was formed by equation (4).Forty patients with CHD were selected for the experimental group.The patients were diagnosed with CHD, had typical changes in biochemical markers of myocardial necrosis, had no hypertension, diabetes, and other cardiovascular, and metabolic diseases, had no sick sinus syndrome, atrial fibrillation, and pre-excitation syndrome, and agreed to this experiment and signed informed consent forms.Patients had a severe mental illness, severe liver and kidney diseases, severe blood disease, and other severe types of heart diseases.Twenty healthy people were selected from recruitment as the CG. The study was approved by the Ethics Committee of the Hospital .The Philips Ie33 color Doppler ultrasound system was for 2DE and RT-3DE examinations. The ultrasound system was equipped with an S5-1 probe, X3-1 matrix 3D probe, and QLAB8.0 image analysis software. The patient was required to rest peacefully for about 10 minutes, and then, lie down on the left side while the chest lead ECG is being recorded. First, the S5-1 probe can routinely examine echocardiographic on the subjects. In the direction of the long axis of the left ventricle, the LVESD and left ventricular end-diastolic diameter (LVEDD) were measured. The four-chamber and two-chamber views were obtained from the cardiac apex to make the endocardium in each view be displayed. Besides, the double-plane Simpson’S method can measure LVEDV and LVESV and calculate LVEF. The above parameters applied the average of three consecutive cardiac cycles.The QLAB8.0 image analysis software can open the images to select the mitral annulus level of the four-chamber and the two-chamber heart views at the apex. The software can measure the heart rate (HR), LVEDV, end-systolic volume (ESV), and ejection fraction (EF);and the ratio of early and late diastolic volume was calculated from end-systole to mitral valve opening image. The sequence analysis was started to automatically obtain the VTC through the software, and the slope of each point on the curve was calculated based on the volume data at each time point of the VTC to obtain the average filling rate (MFR).The standard synchronous 12-lead electrocardiogram was applied to detect all the subjects, and the amplitude and paper speed was set to 10mm/mv and 25mm/s, respectively. The record of each lead was more than six cardiac cycles. Based on sinus rhythm, the vector of PTFV1 referred to the value obtained by multiplying the amplitude of the biphasic P-wave negative phase wave in lead V1 and time, and its unit was mm•s. The measurement of QTd was related to the measurement of QT interval, so the number equaled maximum QT less the minimum QT on the different leads of the synchronized 12-lead ECG. There were synchronization and asynchrony in each lead of the ECG, and the synchronized 12-lead ECG was to observe the waveform of the same cardiac cycle to reduce the influence of heart rate variability on the measured value of the QT interval and to decrease errors.P<0.05.The t-test can compare the means between the two groups, while the one-way analysis of variance was applied to the comparison of the means among multiple groups. Besides, the LSD method was used for pairwise comparison. The linear correlation analysis of binary variables was analyzed with the Pearson method, and the correlation was expressed with the Pearson correlation coefficient. There was a difference with statistical meaning at As shown in P>0.05).Based on the diagnosis results, all subjects were divided into 3 groups: the CG (20 subjects), MIG (19 subjects), and APG (21 subjects). The parameters, including gender ratio, age, and HR of the patients in each group were shown in P<0.05) compared with the CG, while LVEF, E peak, E/A, and E’ peak of the patients in MIG were decreased steeply (P<0.05). The LVESV and E/E’ of the patients in APG were increased hugely (P<0.05), while E peak, E/A, and E’ peak the patients in APG were decreased dramatically (P<0.05). Therefore, there were substantial differences in LVEDV, LVEF, and E/E’ by comparing MIG with APG (P<0.05).In P<0.05) compared with CG, while LVEF and MRF were hugely decreased (P<0.05). LVEDV and LVESV of the patients in APG were also enormously increased (P<0.05) compared to CG, while LVEF and MRF were not changed obviously (P>0.05). Compared MIG with APG, there was a substantial meaning between LVEF and MRF (P<0.05).The LVEDV results measured by the two methods were greatly different (P<0.05), while there were no obvious differences in the results of LVESV and LVEF measured by the two methods (P>0.05).There was a positive correlation between MRF and PTFV1 . However, MRF was negatively correlated with QTd  in LVEDV and LVESV of the patients in MIG were greatly increased (There is a lot of speckle noise in ultrasound images, which greatly affects the accuracy and effectiveness of ultrasound imaging, reduces the quality of the image, and limits the development of automatic diagnosis technology for ultrasound images.Secondly, the difference between the results of quantitative assessment of cardiac function of patients with different methods were analyzed and compared. The results revealed that the LVEDV results measured by the 2DE and 3DE methods were quite different. The negative value of PTFV1 is due to the weakening or obstruction of left ventricular diastolic function in patients with CHD, which leads to a decrease in left ventricular compliance, resulting in a continuous increase in left atrial pressure in patients.20The results demonstrated that 2DE and RT-3DE combined with ECG could effectively examine the changes in LVDF of CHD, and could be applied in clinic. This study provides a simple and easy operatiing process for the detection of LVDF in CHD, which can improve the efficiency of doctors and simplify the patient’s medical process. Due to the limitations of the experimental scale and scope, it was impossible to make effective recommendations for the clinical treatment of CHD. Therefore hopefully this aspect can be covered in future research.


The detection of a congenital heart defect at purchase is an important step in early detection from a clinical and legal standpoint. Indeed, some cardiac abnormalities may be corrected with surgery, and very often, treatment needs to be performed early before congestive heart failure or irreversible heart damage can occur. From a legal viewpoint, if the defect is revealed in a newly purchased puppy, the buyer may be required to return it and receive compensation. Puppies affected with congenital heart defects are likely to die prematurely, causing emotional suffering to the owner. Furthermore, by considering breed predisposition, early recognition allows breeders to avoid breeding from particular dogs with genetic defects and prevent the continuation of genetic defects in breeding lines. Given gaps in the literature about the recognition of murmurs in the puppy trade, the present article describes how to identify a heart murmur in a puppy during a pre-purchase examination and its significance from a clinical and legal viewpoint. In the canine population, the prevalence of cardiac defects ranges between 0.13 and 1.6%. Pulmonic stenosis is the most common defect found in puppies, followed by patent ductus arteriosus, subaortic stenosis, and ventricular septal defect. On the basis of the above considerations, the veterinarian should recognize and identify the murmur following a protocol for routine examination of puppies involved in trade. Buying a puppy is an important step for most pet owners. The prospective owner aspires for the puppy to be healthy and fit well with the new family, often acting on impulse driven by the opportunity and enthusiasm to get a dog. Instead, a pre-purchase examination before selling is strongly recommended in order to evaluate the health status of the animal. The ground rules for a pre-purchase examination are the same as those applicable to clinical evaluation. The cornerstone is to establish the health of the animal or a specific diagnosis which must then be contextualized in terms of a prospective purchaser’s requirements. On the one hand, there are some buyers for whom any risk is acceptable as they do not perceive clinical signs as a problem, but rather as a normal breed-specific characteristic . On the Indeed, heart diseases of proven or suspected hereditary origin in puppies may constitute a defect (vice) in buying and selling, making the animal inappropriate for its intended use, or significantly decreasing its value . In caseEarly identification, therefore, assumes great importance, not only to apply a suitable medical and/or surgical workup and formulate a correct prognosis, but also to prevent any litigation.The diagnostic approach to the discovery of cardiac abnormalities during the auscultation differs in relation to the abnormality detected, the other clinical findings, and the client’s wishes. The innocent murmur is a common physiological finding in puppies, generally as a result of physiologic anemia. Rising hematocrit in growing puppies can explain the spontaneous disappearance of innocent murmurs with aging .Generally, puppies are sold when they are at least 6–8 weeks old to ensure that the puppy has received an adequate supply of milk from the mother dog and has completed the period of socialization.The discovery of an apparently innocent murmur  in a healthy puppy necessitates no more than a follow-up examination at the next appointment for vaccination. Conversely, the detection of a continuous murmur in a puppy requires a complete cardiologic and medical workup.Once the presence of a murmur has been identified, the aim for the veterinarian during the pre-purchase  examination is to determine the existence, severity, and exact origin of the underlying cardiac disease. Furthermore, the veterinarian should be required to perform the necessary diagnostic procedures such as echocardiography, which is considered the initial diagnostic test of choice and gold standard for identifying the cause of a cardiac murmur , and/or Cardiac examination should be performed to evaluate heart rate, rhythm, and the presence of normal and abnormal sounds. Auscultation should be executed in a silent room, with the animal in standing position, auscultating the precordial valve areas in both sides of the chest and, if an abnormal sound is detected, the point of maximum intensity should be identified.Given the gaps in the literature regarding a clinical protocol or guidelines for the identification of a cardiac murmur during puppy trade, the authors describe how to categorize heart murmurs in the animal during a pre-purchase examination and its significance from a clinical and legal viewpoint, as murmurs can be physiological or pathological.decrescendo murmur gradually decreases in intensity. A crescendo—decrescendo murmur is characterized by a gradual increase in intensity, followed by a gradual diminution. A plateau murmur conserves a moderate continuous intensity regardless of their intensity grade. The duration (or timing) indicates the portion of the cardiac cycle that the murmur occupies and not in which the murmur onsets. Murmurs may be systolic , diastolic  or continuous. A continuous murmur initiates during the systole and continues extending on the second sound, throughout diastole or part of thereof. The location indicates areas on the precordium where the murmur is perceived with a higher intensity and correspond at the site of murmur origin  . The ausr origin . When a An innocent heart murmur is found on average in 28% of puppies under the age of 6 months, while in athletic dog breeds such as whippets, it has even higher percentages of up to 58% of puppies ,12. It iAlso called a physiological murmur, a functional heart murmur is caused by an altered viscosity of the blood or by conditions that increase cardiac output, such as: anemia, fever, pregnancy, hyperthyroidism, or increased sympathetic tone. The functional heart murmur has similar characteristics to the innocent murmur but can also occur in adult dogs. It is generally systolic, short, with mild intensity (I–II/VI grade) and PMI focused on the base of the heart .Heart murmurs of intensities greater than III or VI and PMI on the right side, or associated with arrhythmias or clinical symptoms, should be considered as pathological heart murmurs and require further diagnostic investigations .In the canine population, the prevalence of congenital heart disease (CHD) ranges between 0.13 and 1.6% . PulmoniType 1: Dysplasia only affects the valve leaflets, which are fused together but have some mobility, showing a systolic dooming on echocardiographic examination. The aortic/pulmonary trunk diameter ratio is, however, maintained .Type 2: In addition to dysplasia of the pulmonary valve leaflets as in type 1, there is a hypoplasia of the valve annulus with a diameter ratio between the aorta and the pulmonary trunk greater than 1.5 .Pulmonary stenosis (PS) is the most commonly encountered CHD, being described in 11–34% of the total CHD cases in different epidemiological studies ,16,21,22The heart murmur of a pulmonary stenosis is holosystolic, with rough timbre, with PMI on the pulmonary valve focus , poorly or non-radiated, with a “crescendo-decrescendo” pattern. The intensity of the murmur may vary according to the degree of the pathology ,28 Tabl.Patent ductus arterial (PDA) is considered the second largest CHD in dogs, with a rate of prevalence between 8 and 26% ,14,15. R-First degree: Small subvalvular endocardial nodules of a few millimetres forming a limited narrowing. There may be no heart murmur at this stage.-Second degree: The endocardial thickening increases, there is a narrow fibrotic ridge that extends around the left ventricular outflow tract.-Third degree: Subvalvular obstruction becomes a fibromuscular tunnel involving a large portion of the left ventricle outflow tract and also the mitral valve apparatus.Subaortic stenosis (SAS) and aortic stenosis (AS) have a prevalence between 15 and 21% and 5 and 6% of all CHDs in dogs, respectively ,15,16. SThe AS instead presents obstructive lesions to the aortic valvular apparatus; these may include: hypoplastic aortic annulus or thickened leaflets. Similarly, to SAS, AS also causes left ventricle concentric hypertrophy, and post stenotic dilatation of the aorta and aortic valve insufficiency may also be present ,40. The Ventricular septal defect (VSD) is the fourth most common CHD in the canine population, with an incidence between 5 and 14% ,16, whilsecundum septum” originates from the roof of the atria on the right side of the primum septum. Based on the localization, ASDs are then classified in defects of “primum septum” or “secundum septum”. A defect in the development of the “primum septum” results in an ostium low in the atria, below the foramen ovale onsets for a defect localized near the atrioventricular valves. An anomalous development of the septum secundum determines an ostium at or above the level of the foramen ovale [During embryonic development, the atria and the cardiac ventricles communicate with each other, and only later does the interventricular and atrial septa develop, dividing the heart into four chambers. More specifically, the embryologic development of the atrial septum follows the growth of two atrial membranes . The “pren ovale . Similaren ovale ,43. The en ovale . As withen ovale   and mitral valve dysplasia (MVD) have an incidence for CHDs of 3–3.5% and 1.5–2%, respectively. TVD is the most common CHD in Labrador retrievers, and it is transmitted via chromosome 9 by autosomal dominant with incomplete penetrance ,44,45,46MVD is most commonly seen in large-breed dogs, and bull terriers and Great Danes are predisposed. In 36% of cases, the two defects occur together . MVD and-PS: With both infundibular and valvular components, often associated with pulmonary trunk hypoplasia.-Concentric right ventricular hypertrophy: Secondary to the pressure overload due to PS.-VSD: Generally large, it allows a right-left shunt due to the high resistance of the pulmonary circulation.-Dextropositioned aorta .Tetralogy of Fallot (TOF) is a rare defect, accounting for 1–3% of total CHDs in dogs ,17. In tThe atrium and left ventricle are small, and non-oxygenated blood is introduced into the systemic circulation via the VSD. The degree of right-to-left shunting is influenced by the gravity of the PS and the systemic vascular resistance. Right-to-left shunting produces an arterial hypoxemia and an increase in blood viscosity, resulting in an activated erythropoietin production by the kidney ,52.The heart murmur is related to the degree of PS. In the presence of a mild PS and a small VSD, a loud right basilar holosystolic murmur caused by the VSD shunt is audible. Conversely, in the presence of a severe PS associated with a large VSD, and a hyperviscosity syndrome, the murmur may be inaudible ,52 Tabl.In puppies, various hereditary or congenital heart diseases are reported that can have important consequences on animal welfare and health. The diagnosis of CHD is challenging and time-consuming; often, CHDs are diagnosed beyond the legal warranty for vice protection . In factThe early identification of CHDs through murmur audibility can not only avoid legal disputes, but also improve prognosis and treatment. The diagnosis of cardiac murmurs can be challenging, but it represents a valid tool to help the veterinarian practitioner identify CHD early as possible, mostly in predisposed breeds.1.Pre-existing or have a pre-existing cause;2.Hidden  or not easily recognized ;3.Serious or chronic: The defect, in relation its severity, renders the puppy unsuitable for the usage for which it is acquired, to such an extent that the buyer would not have bought it or would have given a lower price if he had been conscious of that.Indeed, a puppy affected with a congenital defect may be considered unsuitable for its specified use. A cardiac defect, due to an anatomic alteration, causes a disorder in normal organic functioning, and inexorably determines a considerable impairment. CHDs may be qualified as a vice, in that the defect is:Taking into account that in the sales process, animals are legally considered as personal property —though tIn fact, in the EU, consumer protection concerning animal purchases is founded on the general consumer protection laws differently than in the US, where there are expressly pet purchase protection laws that vary in relation to the state. These laws allow from as few as 10 days  to up to 2 years  for the detection of the defect  and, necessitate that the clinical examination must be performed within a given number of days of purchase of the dog  so that the buyer may exercise their own rights.An interesting question may be the occurrence that during the animal purchase, the buyer may consider the veterinarian responsible for failing to identify evident clinical signs of cardiac congenital/hereditary defects within the time provided from the law for identification in order to obtain required solutions. In these cases, it is important to follow rules of good practice and a systematic examination protocol, as here reported , that caIn conclusion, the veterinarian should be able to recognize and identify the murmur as in its severity degree and as a possible clinical sign of below congenital heart disease, with the aim of protecting not only the puppy’s welfare, but also the right of the owner.


Patients with heart failure (HF) have high morbidity and mortality. Accurate assessment of right ventricular (RV) function has important prognostic significance in patients with HF. However, conventional echocardiographic parameters of RV function have limitations in RV assessments due to the complex geometry of right ventricle. In recent years, speckle tracking echocardiography (STE) has been developed as promising imaging technique to accurately evaluate RV function. RV longitudinal strain (RVLS) using STE, as a sensitive index for RV function evaluation, displays the powerfully prognostic value in patients with HF. Therefore, the aim of the present review was to summarize the utility of RVLS in patients with HF. Heart failure (HF) is a clinical syndrome with typical symptoms and signs caused by abnormal structure and function of heart . HF is tConsequently, the aim of this review was to summarize the role of RVLS assessed by 2D and 3D speckle-tracking echocardiography in patients with HF, including HF patients with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF).Due to the complex anatomy of right ventricle, correct evaluation of its function requires using multiple parameters, such as TAPSE, S’, RVFAC, 3D RVEF, RVLS and so on. RVFAC is a significant parameter of global RV systolic function, and it is defined as: (RV end-diastolic area—RV end-systolic area)/RV end-diastolic area × 100%. RVFAC reflects longitudinal and radial information of RV systole, which overcomes the shortcoming that only confines to a single type of motion. It is associated with RVEF derived from CMR, and can provide prognostic information in patients with HF . However3D RVEF reflects longitudinal and radial components of RV systole, which overcomes the geometric limitations of traditional echocardiography parameters for evaluating RV function. 3D RVEF can explore the entire right chamber including RV outflow tract, which can include the contribution of RV outflow tract to global systolic function. It is a global measurement of RV systolic function, however, it cannot directly represent systolic performance for the reason that it depends on load and reflects the interaction between systole and load. In addition, this technique depends on adequate image quality, requires offline analysis and experience, and is time-consuming, which limit its widespread application in clinical practice ,35.Tissue Doppler imaging (TDI) has traditionally been used to measure blood flow velocities, and it can also be used to measure myocardial and other tissue velocities, which can provide significant information about cardiac function. Strain measurement is based on myocardial velocity gradient, which is an estimate of strain rate, and therefore strain can be calculated as the temporal integral of strain rate. Strain and strain rate are measured in the apical view, where there is favorable myocardial motion along the ultrasound beam . TDI-derIn recent years, two-dimensional speckle tracking echocardiography (2D-STE) has been developed as a new imaging tool of evaluating cardiac function. 2D-STE is the two-dimensional tracking of unique speckle patterns created by the constructive and destructive interference of ultrasound beams within myocardial tissue . 2D-STE In addition to the information of myocardial motion along the direction of ultrasound beam, information on myocardial torsion, circumferential and radial motion can also be obtained by 2D-STE. STE represents a relatively rapid, high feasibility and easy-to-perform imaging tool to estimate RV function . In contHowever, intrinsic limitations of 2D-STE should be addressed. First, 2D-STE analysis requires good image quality, which produces less accuracy in endocardial border definition and tracing in patients with suboptimal image quality. Second, cardiac motion is three-dimensional in nature, and the myocardial deformation in 2D plane measured by 2D-STE has out-of-plane motion of speckles. Moreover, the software for RV strain analysis that we use are designed for left ventricle (LV) strain evaluation; the dedicated software for RV strain measurements has not yet been released. Finally, RV strain values depend on vendor and software versions .More recently, three-dimensional speckle tracking echocardiography (3D-STE) has been introduced as a novel technique than can track the myocardial motion within the 3D volume. Thus, 3D-STE is free of geometric assumptions and out-of-plane motion of the speckles, allowing a more accurate and comprehensive evaluation of myocardial function owing to overcoming the limitations of 2D-STE ,38,65,66The main methods of evaluating RV strain by CMR imaging include CMR tissue tagging, CMR feature tracking (FT) and CMR tissue tracking (TT). FT is an image postprocessing technology which is applied retrospectively to routinely acquired cine images for strain measurements. After user-defined epicardial and endocardial borders are delineated, endocardial features were tracked by FT software. Except for GLS, which is measured on three long-axis cine images, both global circumferential and radial strain are derived from short-axis cine images. The structure and function of myocardium can be evaluated from different directions by CMR, which has the advantages of multi-parameters and high resolution and is considered as the gold standard for the assessment of the structure and function of right ventricle . Yet, CMImpaired LV diastolic function is the main manifestation in the early stage of HF, while the systolic function is normal or slightly decreased, namely HFpEF (LVEF ≥ 50%); with progress of the disease, cardiac function is gradually decompensated and LV systolic function is impaired, namely HFrEF (LVEF < 40%) ,75. WhenRV dysfunction is common and often leads to poor prognosis in patients with HFpEF. Based on the different research methods, sample sizes and diagnostic criteria, the prevalence of RV dysfunction in patients with HFpEF fluctuates greatly. However, at least 20% of patients with HFpEF are known to have RV dysfunction, and the incidence of RV dysfunction can be potentially up to 30% to 50% ,75,76. TLejeune et al.  found thGiven the complex geometry of the right ventricle, RV longitudinal strain may be most accurately evaluated by 3D-STE. Until now, there have been limited studies regarding the utility of 3D-STE in RV assessment in clinical practice. A study  by Meng Kucukseymen et al.  evaluateRV dysfunction is often present in patients with HFrEF. The current findings regarding RV longitudinal strain in patients with HFrEF are shown in RV strain was a significant predictor of long-term adverse outcomes. Moreover, RV strain ≥ −14.8% independently predicted adverse events after adjustment for age, LVEF, RV s’, E/e’ septal, and right atrial volume index . TherefoSeveral studies have reported the predictive value of RV longitudinal strain in HF patients with preserved conventional RV systolic function parameters, such as TAPSE and S′. However, these traditional RV function indicators could not accurately assess and represent global RV systolic performance because they only reflected segmental function of the right ventricle ,88. RVLSp = 0.01). Meanwhile, left-sided indices cannot provide prognostic information of unfavorable outcomes. Hence, 2D-RVFWLS played a crucial role in identifying patients with acute HF at higher risk for cardiac events after discharge. Additionally, the author also demonstrated that 2D-RVFWLS was a more accurate marker of RV systolic function than 2D-RVGLS. Yao et al. [Repeated rehospitalization and adverse outcome are usually experienced by patients with HF, and therefore, it is vital to identify vulnerable HF patients at high risk of poor prognosis among patients hospitalized because of acute HF. The current results of RV longitudinal strain in acute HF are depicted in o et al.  found tho et al.  showed to et al. . Patiento et al. .p = 0.0037).Nonischemic dilated cardiomyopathy (NIDCM) is the most common form of cardiomyopathy, and the major cause of HF in addition to hypertension and coronary diseases. It is defined as LV systolic and diastole dysfunction in the absence of load abnormality or coronary artery disease . RV dysfMF is a common pathological manifestation in patients with end-stage HF, and is able to result in cardiac remodeling, increased myocardial stiffness, and pump failure. Therefore, early and accurate identification of MF has significant clinical implications for assessing the progress of the disease, response to the treatment, and prognosis in patients with HF. The current results of RV longitudinal strain and myocardial fibrosis in patients with end-stage HF are shown in LV assist device (LVAD) is one of the treatments for patients with end-stage HF. As a bridge to transplantation, LVAD helps to improve organ function, quality of life and clinical outcomes. RV failure following LVAD implantation remains a major cause of higher morbidity and mortality ,104,105.RV contractile reserve is a new echocardiographic parameter that has emerged in recent years, which is also of vital importance to evaluating the outcomes of HF patients. It is defined as the capability of the RV to adapt to the increased pulmonary vascular resistance and is regarded as a sensitive index of volume load, which reflects the dynamic function of the right ventricle ,111. It a et al.  examinedIn recent years, RV strain has been regarded as a new echocardiographic parameter for the prognostic assessments of patients with cardiovascular diseases , which iChemotherapy is one of the most effective treatments of cancer at present. However, cardiotoxicity is one of the most devastating complications of cancer treatment and has become the main risk factor for prognosis of cancer patients. Therefore, careful monitoring of ventricular function plays important role in the treatment process . The curRV function can offer important clinical and prognosis information in various clinical settings. RVLS, as a new echocardiographic parameter, provides a more comprehensive and detailed evaluation of RV systolic function, allowing for an early detection of subclinical RV dysfunction. Furthermore, RVLS has been regarded as an independent predictor of poor prognosis in patients with HF, regardless of LVEF. RVLS also can provide superior value of prognosis in nonischemic dilated cardiomyopathy, congenital heart diseases and chemotherapy cardiotoxicity. Thus, it is a powerful index for identifying patients who are at higher risk among HF patients and other cardiovascular diseases. Nevertheless, further studies are essential to determine its role in the management of patients.


Aims: Assessing the effectiveness of novel bio-sensing technology (CardiacSense), for accuracy and reliability of automatic detection of life-threatening arrhythmias.Methods and Results: This prospective study consisted of Eighteen patients  undergoing induction of ventricular tachycardia/fibrillation or provocation of transient ventricular asystole. We tested the detection of provoked ventricular arrhythmias by a wrist-worn watch-like device which uses photoplethysmography (PPG) technology to detect the cardiac rhythm. We used simultaneous electrocardiographic (ECG) recordings as gold standard for arrhythmia definition and confirmation of beat-to-beat detection. A total of 1,527 QRS complexes were recorded simultaneously by ECG and PPG. The overall correlation between the ECG  and the PPG  was high, with a correlation coefficient of R = 0.949 (p < 0.001). The device accurately detected all events of mimicked life endangering arrhythmias, including five events of transient (adenosine-induced) ventricular asystole as well as seven episodes of monomorphic ventricular tachycardia and 6 events of ventricular fibrillation.Conclusion: This proof-of-concept study suggests that wearable devices using PPG technology, currently used to detect atrial fibrillation, may also have a role as automatic detectors of life-threatening arrhythmias. Out of hospital sudden cardiac death (SCD) is very common worldwide and accounts for more than 5% of all crude mortality in the United States . DespiteA major predictor of prognosis in SCA is response time, provision of cardiopulmonary resuscitation and a witnessed event . It is tA continuous heart-rate monitoring device, comfortable enough to be worn all of the time and reliable enough to detect potentially life-threatening arrhythmias, could trigger the alarm that would start the chain of survival thus offering a better prognosis when a SCA occurs. We report here of our study with such a device, that uses photplatysmogrphy (PPG) technology, tested on patients with induced arrhythmias in a controlled setting as surrogate for life-threatening ventricular arrhythmias. Of note, heart-monitors using PPG technology are already in use for the detection of atrial fibrillation –11. HoweThis is a single-center, prospective study, assessing the effectiveness of novel bio-sensing technology (CardiacSense), for accuracy and reliability of automatic detection of life-threatening arrhythmias. The same PPG devices have been used to continuously detect sinus rhythm in ambulatory volunteers  and for The study-group consisted of consecutive patients undergoing electrophysiological studies (EPS) or defibrillator implantation [with ventricular tachycardia/fibrillation (VT/VF) induction] or ablation procedures that included adenosine injection (provoking transient ventricular asystole). The study was approved by our Institutional Review Board (IRB number TLV 0066-16). All patients provided informed consent. Importantly, all the electrophysiologic studies performed during the course of the study, and all the attempts to provoke arrhythmias during the course of these procedures, were clinically indicated. For example, intravenous injection of high doses of adenosine (invariably provoking transient ventricular asystole due to sinus arrest or transient atrioventricular block) is standard practice during ablation of atrial fibrillation to test for pulmonary vein reconnection.The CardiacSense is a wrist-worn watch-like device, specifically designed to detect cardiac arrhythmias. PPG is a simple optical technique that can be used to detect blood volume changes in the microvascular bed of tissues. Using this technology, it is possible to accurately detect the pulse rate and pulse pressure on a beat-by-beat basis. PPG is used for atrial fibrillation detection by other manufacturers, including the Apple Watch –11.The algorithm that detects a life-threating arrhythmia is based on two parameters: The first is the length of the RR interval , in order to detect episodes of predefined extreme bradycardia or tachycardia. The second, uses the signal to noise ratio of the PPG measurements, which correlates with the pulse pressure and thus correlate with cardiac output and tissue perfusion pressure. Prospective participants underwent simultaneous, continuous PPG (CardiacSense watch placed on the wrist) and ECG recordings during the entire procedure. The ECG recording was the gold standard used for analyzing the simultaneous PPG recording. Specifically, all cardiac intervals in ECG recordings  are compared with the quasi-simultaneous (delayed by a few milliseconds) PPG signals  . Time tot-test. Accuracy was determined using the Pearson correlation test. Significant p-values were considered when p < 0.05. All calculations were done using SPSS v.24 from IBM, Armonk, Virginia.All data is summarized and displayed as number (and percentage) for categorical variables. Differences between RR and GG intervals was compared using the paired sample Eighteen patients  participated in the study of simulated cardiac arrest events that were recorded with simultaneously with PPG and ECG . The eveDuring electrophysiological studies and defibrillation threshold testing (DFT), 7 VT events and 6 VF events were induced, all of which were detected by the PPG algorithm. Representative examples are shown in Adenosine test provoked 5 transient ventricular asystole events, all of which were detected by the PPG algorithm. Representative examples are shown in R = 0.949 (p < 0.001). There was a small but statistically significant difference between RR and GG intervals: the former being, as a group, shorter than the simultaneously recorded G-G intervals by 16.9 ± 209 msec, p = 0.002. Of note, these results do not apply to the VF and rapid VT episodes that appeared as “asystole” in the PPG recorder.A total of 1,527 QRS complexes were recorded simultaneously by ECG and PPG during EPS, out of which 522 (34.2%) were recorded during procedures involving adenosine testing for provocation of asystole, 320 (20.1%) during procedures involving VF provocation and 685 (44.9%) during VT provocation. The overall correlation between the R-R and the G-G intervals was high, with a correlation coefficient of Out of the 18 events of cardiac arrest, all were detected by the PPG algorithm yielding a sensitivity of 100%. However, all VF episodes and one episode of rapid monomorphic VT were detected as “asystolic arrest” (rather than tachyarrhythmia-related arrest) due to absence of minimal amplitude PPG signals during tachyarrhythmias causing low- or no cardiac output.This proof-of-concept study suggests that wearable devices using PPG technology, currently used to detect atrial fibrillation –11, may Automatic arrhythmia detectors could draw the attention of household members  with visual and audible alarms. The device could not only alert bystanders to an event of serious nature but could also instruct them to preform CPR, as this is often delayed even in populated settings. Furthermore, automatic arrhythmia detectors could communicate via mobile phone or Wi-Fi with Emergency Medical Services, providing them with PPG recordings of the event and with the patient's exact location. Automatic detectors of life-threatening arrhythmias could ultimately be designed to interact with drone networks delivering automatic external defibrillator (EAD) devices. A remaining concern remains the issue of false alarms.The possibility of excessive false alarms must be addressed. With the newest generation of the Apple-Watch, which offers the possibility of ECG confirmation after automatic detection of atrial fibrillation by PPG sensors , there were no events of false-positive detection of atrial fibrillation . To our Our study has several limitations. The number of arrhythmic events tested was small. However, as a proof of concept, and knowing that each ECG signal triggers cardiac output that, in turn, triggers a PPG signal, it is fairly clear that additional arrhythmic events will add little information. A more important limitation relates to the fact that all patients were studied while resting, sedated, in a supine position. It remains to be demonstrated that arrhythmia detection is reliable in ambulatory and active patients. However, this particular PPG sensor has been shown to detect cardiac rhythm with fair accuracy in ambulatory patients in sinus rhythm . FinallyThe results of this proof-of-concept study suggest that PPG-based arrhythmia detectors, currently in use for the detection of atrial fibrillation, could be of use of the immediate detection of life-threatening arrhythmias.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.The studies involving human participants were reviewed and approved by Tel Aviv Medical Center. The patients/participants provided their written informed consent to participate in this study.EC, AH, AS, GM, SV, and RR have all participated in the data acquisition, study design, and writing of the research. All authors contributed to the article and approved the submitted version.GM designed the detection algorithm for CardiacSense. SV is Chief Medical Officer for the cardiac arrhythmia section at CardiacSense. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


To assess the impact of regurgitant jet direction on left ventricular function and intraventricular hemodynamics in asymptomatic patients with bicuspid aortic valve (BAV) and mild aortic valve regurgitation (AR), using cardiac magnetic resonance (CMR) feature tracking and 4D flow imaging. Fifty BAV individuals were retrospectively selected: 15 with mild AR and posterior regurgitation jet (Group-PJ), 15 with regurgitant jet in other directions (Group-nPJ) and 20 with no regurgitation (Controls). CMR protocol included cine steady state free precession (SSFP) sequences and 4D Flow imaging covering the entire left ventricle (LV) cavity and the aortic root. Cine-SSFP images were analyzed to assess LV volumes, longitudinal and circumferential myocardial strain. Circumferential and longitudinal peak diastolic strain rate (PDSR) and peak diastolic velocity (PDV) were reduced in group PJ if compared to group nPJ and control group , whereas no differences have been found in systolic strain values. 4D Flow images (available only in 9 patients) showed deformation of diastolic transmitral streamlines direction in group PJ compared to other groups. In BAV patients with mild AR, the posterior direction of the regurgitant jet may hamper the complete mitral valve opening, disturbing transmitral flow and slowing the LV diastolic filling. Bicuspid aortic valve (BAV), with a prevalence of 0.5–2% of the general population , includeThe characteristics of the regurgitant jet and its severity in BAV patients can be highly heterogeneous, as they depend on valve phenotype, cusps asymmetry, aortic root dilation and acquired abnormalities  , 6. ModeSpecifically, in some cases the regurgitant jet is directed posteriorly against the anterior mitral leaflet, interfering with the valve opening , 10, andThe advanced analysis of cardiac fibers deformability offered by the Cardiovascular Magnetic Resonance (CMR) feature tracking (CMR-FT) technique enables the accurate and reproducible assessment of early modifications in both LV systolic and diastolic function –13. CMR-Moreover, the four-dimensional flow (4D Flow) imaging, obtained by acquiring 3D phase contrast images with three-directional velocity encoding, enables to investigate intraventricular blood flow dynamic in normal and pathological conditions .The purpose of our study was to assess the impact of the regurgitant jet direction on left ventricular function and intraventricular hemodynamics in asymptomatic patients with BAV and mild insufficiency.We retrospectively selected a cohort of 50 individuals with BAV, who referred our Institution for their periodic follow-up monitoring, between January 2010 and December 2020. CMR exams were selected in order to compose three age- and body surface area (BSA) -matched groups:Posterior Jet or PJ Group) and 15/30 with a regurgitant jet directed to other directions (Non-Posterior Jet or nPJ Group).Thirty subjects had mild valve regurgitation: 15/30 with a posteriorly directed jet against the anterior mitral leaflet (Controls).Twenty subjects without any regurgitation or with a negligible degree of regurgitation , atrial fibrillation, autoimmune diseases, diabetes, other concurrent known congenital heart disease, genetic syndromes (Turner or Marfan) or cardiovascular disease. We also excluded patients with mitral valve insufficiency or stenosis.Grading of aortic stenosis and insufficiency was assessed by color-Doppler evaluation at echocardiography.Before CMR scanning, an anamnestic evaluation and clinical parameters were also collected .CMR images have been acquired on a 1.5 T  and a 3.0 T  scanners, both located at the Policlinico Umberto I Hospital of Sapienza University of Rome.CMR protocol included 2D ECG-gated cine-SSFP images in the short-axis plane covering the entire LV cavity (a stack of 8–10 contiguous slices from the base to the apex) and in two, three and four chambers views, to quantify ventricular size and function and to obtain a complete ventricular function assessment.A stack of 4 to 6 contiguous cine-SSFP images oriented orthogonal to the longitudinal axis of aortic root covering from aortic annulus to sinotubular junction was acquired in order to analyze valve morphology and function and to measure aortic root diameters.2, slice thickness 6mm, interslice gap: 2mm in-plane resolution 1.25 × 1.25 mm2, Velocity Encoding or VENC: 150 cm/s).Cine-SSFP images were performed with a slice thickness of 6 mm for the aortic root and 8 mm for the LV, with no overlap and no gap for the aortic root and an interslice gap of 2 mm for the LV . A stack of three 2D phase-contrast (PC) images oriented parallel to aortic root  was acquired to analyze transaortic flow velocities  at a flow of 1.5 ml/s; subtracted images were reconstructed to eliminate background signals.Within the total cohort, we selected a sub-group of 9 pts that also performed a 4D-Flow CMR: 3 of them belonging to PJ group, 3 of them to nPJ group and 3 to the control group.Those patients have been scanned at the 3.0 T magnetic resonance unit using a three-dimensional flow-sensitive gradient-echo pulse sequence, acquired in the oblique-sagittal orientation to encompass thoracic aorta and the entire LV cavity, during free breathing using a respiratory navigator in 20 phases/cardiac cycle.3; VENC range had been properly tailored as the lowest value avoiding aliasing, generally 150 cm/s; acquisition time of the 4D Flow sequence ranged from 15 to 20 min based on the heart rate and breathing rate .4D Flow sequences (3dcine_ktarc_WIP package) were performed with the following parameters after gadolinium-based contrast administration: RT = 4.3–5.27 ms, ET = 2.02–2.15 ms, FA = 10–14°, voxel size = 1.48 × 1.48 × 1.8 mmBAV type classification was performed according to Sievers’ classification . MaximumTwo operators in consensus with 14- and 18- year-old experience in CMR imaging  visually evaluated the presence and the direction of diastolic aortic valve regurgitant jet.Aortic trans-valvular flow was, then, quantitatively measured using PC sequences (2D and/or 3D when present) to assess the peak of maximum velocity (Vpeak) and aortic valve area, in order to classify the aortic stenosis degree, and the regurgitation fraction (RF), defined as the ratio between regurgitant volume and stroke volume. We enrolled only patients with a aortic valve Vpeak < 250 cm/s and RF < 29%, whereas in control group the RF was lower than 5%. Trans-valvular aortic flow was assessed also on 4D Flow images, when acquired. In case of discordance between measurements obtained by 2D PC and 4D Flow datasets, the highest values were considered. All patients satisfied the inclusion criteria both when assessed by 2D PC and 4D Flow images.LV volumes measurements were performed using a dedicated software . LV endocardial and epicardial contours were manually traced on short-axis cine-SSFP images in all the phases of cardiac cycle . AnalysiThe 2D tissue tracking analysis was assessed using mid-ventricular short-axis, vertical- and horizontal long-axis cine-SSFP images. The epicardial and endocardial contours were drawn at end-diastolic phases. Our software (Tissue Tracking module) was able to generate a pixel-intensity map for a small region of the myocardium on cine-SSFP images, using algorithms to identify the most similar patterns of pixel-intensity on images from all subsequent images in the cardiac cycle to “track” a specific point in the myocardium. Myocardial tracking was visually reviewed and the contouring errors in tracking the myocardial borders were corrected before repetition of the analysis.We measured circumferential (c-) and longitudinal (l-) components of the different LV strain parameters in order to detect any alteration in myocardial fibers deformability during the systolic and diastolic relaxation phases: peak systolic strain (%), peak systolic strain rate (%/s), time to peak strain (s), peak diastolic strain rate (%/s), peak diastolic velocity (mm/s).Circumferential strain values were calculated as the mean of values measured on three mid-ventricular short axis views in order to warrant adequate reproducibility of measurements and representativeness of myocardial contractile dysfunction.Longitudinal strain values have been obtained as the mean of strain values measured on vertical- and horizontal long-axis.4D Flow data have been automatically processed by using a dedicated commercially-available software  in order to assess intraventricular instantaneous velocity vectors and to generate path-lines and streamlines dynamic graphs. 4D Flow data were automatically processed through prefiltering of velocity components to correct for eddy current errors and aliasing and to decrease signal noise. The path-lines and streamline maps have been elaborated using ventricular long axis projections on the background  and the most representative time-frame of mid-diastolic phase was selected in order to identify the predominant orientation axis of transmitral diastolic flow.We also analyzed the left intraventricular flow using path-lines in order to understand whether the aortic valve regurgitation had a macroscopic impact on flow pattern and mitral valve kinetics.2) test was performed. All the tests were 2-tailed, and only P values < 0.05 were considered statistically significant. Analysis was performed using SPSS software version 26.0 (IBM).All the data are presented as counts and percentages for categorical data and means ± standard deviation for continuous data, whose distributions were tested for normality using Shapiro-Wilk test. CMR and clinical parameters comparisons were undertaken using the one-way analysis of variance (ANOVA) with Bonferroni’s post-hoc test for normally distributed values or Kruskal-Wallis test with Bonferroni’s post-hoc test for non-normal distributions. For categorical data the Chi-square (XOur population was mainly composed of adolescent and young adult (age: 24.4 ± 11 years-old), with a prevalence of male gender .No significant differences have been found among three groups in mean age, BSA and body mass index (BMI).The only BAV phenotypes represented in PJ group were type 1 R–L (67%) and type 1 R–N (33%) . The same result was found for the longitudinal peak diastolic strain rate , that was significantly lower in PJ group as compared to nPJ group and control group.LV strain results were associated to a decreased circumferential peak diastolic velocity  and longitudinal peak diastolic velocity  in PJ group, as compared to the other two groups  was found in PJ group. Notably, PJ group showed the longest TTPFR value , reflecting an elongation of the early diastolic phase.PJ group showed greater aortic annulus diameters than the control group , with no significant differences in the comparisons between PJ Vs nPJ group (p: 0.164) and nPJ Vs control group (p: 0.383).The visual analysis of path-lines dynamic graphs demonstrated an angulation of the predominant axial orientation of the trans-mitral diastolic flow as compared to the LV longitudinal axis in all PJ subjects. Whereas nPJ subjects and controls showed a complete alignment of the two axes in all cases.The aortic regurgitant jet was depicted by path-lines maps in all PJ cases and 1/3 nPJ case, while in 2/3 nPJ cases it was not clearly distinguishable. In all three PJ subjects, the regurgitant jet clearly hampered the opening of the mitral valve, causing an abnormal angulation and eccentricity of the transmitral flow , the inversion of the pressure gradient between the left atrium and ventricle and relaxation of the ventricular wall cause the opening of the mitral valve, allowing the rapid filling of the ventricle (rapid isotonic diastole).When posteriorly directed, the eccentric regurgitant jet may hinder normal anterior mitral leaflet mobility causing a fluttering of the valve leaflet and delayed opening , resultiIndeed, in our study, PJ group had a delay in peak filling (increase TTPFR), even there were no differences in terms of PFR among three groups.In cases of moderate-to-severe chronic AR this mechanism may induce asymmetrical mitral valve (MV) remodeling , with enDiastolic dysfunction, defined as an increased resistance to filling by the LV , can be In our population, PJ patients had both increased end diastolic and systolic LV volumes as compared to nPJ and controls, whereas there were no differences between nPJ and controls, highlighting how the direction of the jet can affect the ventricular filling volumes, even if the regurgitation is not severe enough to cause volume overload.The early identification of subclinical diastolic dysfunction in BAV patients with preserved ejection fraction and mild AR may be benefical for improving their risk stratification and predict long-term outcome.In fact, diastolic dysfunction represents the first altered parameter in the progressive process that may finally result in HF. It is known that the 5-year mortality rate for individuals with HF, preserved ejection fraction and diastolic dysfunction, ranges between 55 and 74% .per se leads to a greater incidence of cardiovascular complications as compared to the general population  [Moreover, BAV condition schemia) –28. FurtThe use of CMR-FT to evaluate LV diastolic impairment has already been performed in asymptomatic patients with BAV and preserved ejection fraction , evidencFinally, the use of 4D Flow imaging technique offered a deeper insight on the hemodynamic consequences on intraventricular flows of different patterns of regurgitation jet.As explained in in-vitro studies conducted on insufficient aortic valves, the presence of a regurgitation jet generates an anticlockwise intraventricular vortex which hampers LV filling, as the degree of regurgitation increases, interacting with the clockwise vortex coming from the mitral valve , 31. We Indeed, according to our 4D Flow imaging analysis, in PJ group the AR jet deviates the transmitral inflow from the normal direction towards the inferolateral wall, likely increasing local wall stress and influencing intraventricular vortex formation. Conversely, in nPJ group the transmitral diastolic flow direction was preserved with main orientation parallel to the LV longitudinal axis.The proper vortices generation seems to have a crucial role in the dynamic balance between rotating blood and myocardial tissue contractile activity. Maladaptive intracardiac vortex dynamics may modulate the progressive remodelling of the left ventricle towards cardiac dysfunction (32).Further 4D flow imaging studies could offer new perspectives to better understand the effect of aortic valve abnormalities not only on downstream flow (33), but also within the ventricular cavity.Actually, AR is classified by a combination of clinical signs, LV function and size, and aortic regurgitation degree . HoweverIn our analysis, the presence of posterior jet was most frequently related to the type I L–R configuration where the conjoined cusp was often responsible for the prolapse causing the posteriorly directed jet .Moreover, the type I L–R configuration is the most frequent form of BAV phenotype, therefore a posterior jet is also a relatively frequent finding.Finally, given that the AR recurrence after BAV repair is not rare, surgical planning should consider those phenotypes associated to greater risk of residual posteriorly directed jet.Another aspect of interest would be the evaluation of jet direction effects on intraventricular hemodynamics, during physical or pharmacological stress. Some studies conducted on BAV athletes with mild AR noticed an increase in LV diameters in BAV as compared to tricuspid aortic valve subjects, but LV volumes were within the normal range . How theOur study could be limited by the relatively small sample size of the population, which did not allow the analysis of correlation with the different bicuspid phenotypes. In addition, the low number of individuals who underwent 4D Flow imaging prevented us to elaborate quantitative comparison analysis on 4D Flow data.We also recognize that the lack of follow-up data did not allow defining the long-term clinical relevance of these phenomena in terms of valve disease progression, ventricular remodeling and ventricular function deterioration. Furthermore, this study did not include other CMR features able to assess the diastolic dysfunction, such as the assessment of transmitral valve flow or through the pulmonary veins , 35, whiIn conclusion, the posterior regurgitation jet direction is associate to the presence of a subclinical diastolic dysfunction in BAV patients with mild AR and preserved ejection fraction. The identification of an early stage of diastolic dysfunction with strain imaging could improve the future management of those patients and prevent the worsening of their clinical condition.