Atrial standstill (AS) is a rare condition defined by the lack of atrial electrical and mechanical activities. It is usually clinically manifested as symptomatic bradycardia, which requires permanent pacemaker (PPM) implantation. Traditional right ventricular apical pacing causes electrical and mechanical dyssynchrony resulting in left ventricular dysfunction, heart failure, and arrhythmias. As a novel physiological pacing strategy, left bundle branch area pacing (LBBaP) has demonstrated effectiveness and safety in recent years, but its application in exceptional conditions is rarely reported. We report the case of a 47-year-old female, who was diagnosed with AS complicated with a giant atrium, and successfully received a single-chamber PPM with LBBaP. Atrial standstill (AS) is a rare type of arrhythmia characterized by the loss of electrical and mechanical activities of the atrium , 2. ElecA 47-year-old female patient was admitted with recurrent syncope for 2 days. Bedside ECG on admission discovered no visible P waves or atrial fibrillatory waves, ventricular escape rhythm with ventricular rate 40–45 bpm, and torsade de pointes. Bedside echocardiography indicated an enlarged heart dominated by the atrium, where the right atrium (RA) size was 8.9 cm × 5.6 cm, the left atrium (LA) size was 7.2 cm × 5.6 cm, the left ventricular end diastolic diameter was 5.1 cm, the left ventricular ejection fraction (LVEF) was 50%, and there was extensive tricuspid regurgitation . MoreoveEMD, SCN5A, and MYL4 , including selective left bundle branch pacing (LBBP) and non-selective LBBP. The active lead is twisted through the septum from the right ventricular septum to the left fascicular branch area under the intima of the left ventricular septum, and the pacing captures the left Purkinje network to circumvent the blocked site and maintains the electrical synchronization of the left ventricle –24. LBBadynamics . LBBaP wdynamics . Severaldynamics . For patdynamics –35. In adynamics . Anotherdynamics .Huang et al.  expoundeIn summary, when PPM treatment is essential in AS with a giant atrium, LBBaP is a promising pacing strategy and the technique should not be waived prematurely. In this case, LBBaP was successfully achieved by HIS sheath shaping, and the intraoperative and postoperative parameters were satisfactory and stable. Further follow-up observation is indispensable to assess the stability, safety, and clinical prognosis. This clinical experience in such exceptional circumstances justifies further investigation.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.JinZ and QJ contributed to the conception of the study. JinZ wrote the manuscript. QY, JiaZ, and QC helped to analyze the patient data and curate the data. QJ helped to perform the analysis with constructive discussions. All authors contributed to the article and approved the submitted version.The 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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Atrial septal defect (ASD) results in a left‐to‐right shunt causing right‐ventricular (RV) volume overload and decreased cardiac output from the left ventricle. Pressure–volume (PV) loops enable comprehensive assessment of ventricular function and might increase understanding of the pathophysiology of ASD. The aim of this study was to investigate if left‐ventricular (LV) haemodynamic response to stress in patients with ASD differs from controls.n = 18, age 51 ± 18) and healthy controls  underwent cardiac magnetic resonance (CMR) and brachial cuff pressure measurements at rest and during dobutamine stress. An in‐house, validated method was used to compute PV loops.Patients with ASD . Stroke work and external power increased and potential energy decreased during stress in patients  and controls . Contractility and arterial elastance at rest were higher in patients than controls . Contractility increased during stress in both groups . There was no difference between patients and controls in arterio‐ventricular coupling.Patients had lower stroke work, potential energy and external power at rest than controls (LV haemodynamic response to stress can be assessed using noninvasive PV loops derived from CMR and brachial blood pressure. Patients with ASD had normal LV energy efficiency, in contrast to other patient groups with decreased cardiac output. Data suggest that patients with ASD had an increased inotropic level at rest with high contractility and heart rate but were able to respond with a further increase during stress, albeit to not as high a cardiac output as controls. Short‐axis balanced steady‐state free‐precession (bSSFP) cine images covering the entire heart were acquired with retrospective ECG gating. Typical imaging parameters were: acquired temporal resolution 45 ms reconstructed to 30‐time phases per heartbeat; TE/TR 1.4/3 ms; flip angle 60°, slice thickness 8 mm with no gap. Two‐dimensional free‐breathing, through‐plane phase‐contrast (PC) flow measurements were performed in the ascending aorta and pulmonary artery. After examination at rest participants received dobutamine intravenously at 10 µg/kg/min for 3 min, thereafter increased to 20 µg/kg/min. To reach 70% of the predicted maximal heart rate, defined as 220 minus the subject's age, 0.25–0.75 mg of atropine was added if needed after 3 min with dobutamine of 20 µg/kg/min. When the target heart rate was reached, the same images as at rest were acquired. The dobutamine infusion was ongoing during the acquisition of MR images and the heart rate kept above 70% of the predicted maximal heart rate. Blood pressure and heart rate were measured regularly during the examination to assure a steady stress level.2.3http://segment.heiberg.se) was used, with an in‐house method for the analysis of PV loops  was registered. To ensure maximal exertion, patients were encouraged to continue until the respiratory exchange ratio was 1.1 or more. Twelve‐lead ECG was recorded continuously, and blood pressure was measured manually using a Doppler at rest and every minute during exercise. Peak VO2 was presented as ml/min/kg, and as a percentage of the predicted value. Reference values for peak VO2 were obtained from the Study of Health in West Pomerania (SHIP)  on a cycle ergometer  before the magnetic resonance imaging (MRI) or the day after. The protocol was individualized with incremental increases in workload until exhaustion, at which point peak oxygen uptake . Continuous variables are presented as mean ± standard deviation or median [IQR] according to normal distributions and categorical variables as absolute numbers and percentages. Student's 3p < 0.01) and had normal predicted oxygen uptake compared to reference values . Mean ASD diameter was 15.3 ± 1.3 mm and mean cross‐sectional area indexed to body surface area was 1.0 + 0.2 cm2/m2. Patients had lower LV end‐diastolic volume (p < 0.0001) and end‐systolic volume (p < 0.01) at rest than controls. There was a correlation between age and Ea and Ea/Emax in controls , but not in patients   but not in controls . No other parameters correlated with age in either ASD patients or controls.Characteristics and cardiac volumes of patients and controls are shown in Table 2 in patients  but not in controls . Peak VO2 did not correlate with any other PV‐loop derived parameters either in ASD patients or controls , but no correlations with other PV‐loops derived parameters were seen . Thus, Emax depends on the intrinsic contractility of the myocardium but is also influenced by the anatomical remodelling of the ventricle. Thus, the higher Emax at rest in patients with ASD is likely due to the chronic underfilling of the left ventricle and smaller size of the left ventricle as well as a higher inotropic state. The higher Emax seen in both patients and controls during stress is likely attributed solely to increased myocardial contractility due to increased sympathetic tone. The normal response to stress seen in patients with ASD contrasts with patients with heart failure with preserved ejection fraction. These patients also have higher Emax at rest but in contrast to patients with ASD, they have a blunted increase during stress, due to low intrinsic myocardial function (Kawaguchi et al., The definition of myocardial contractility has been extensively discussed over the years (Davidson & Giraud, 4.3Arterial elastance was higher in patients than in controls. Ea correlates with age (Chen et al., 50 to be zero, an approximation that may not be correct, but validations have shown good agreement between model‐derived measures and in vivo measurements, and so this approximation is judged to be acceptable (Seemann et al., 2 or age and some of the PV‐loop derived parameters suggesting this most likely would not affect the overall conclusions of the study. There were also differences between the groups in the distribution between men and women and this may potentially influence the results (Hayward et al., The method used to obtain PV loops requires unobstructed communication between the left ventricle and the brachial artery. In this study, no patients or controls had signs of stenosis, and so this limitation most likely does not influence the results. The method assumes V6LV haemodynamic response to stress can be assessed using noninvasive PV loops derived from CMR and brachial blood pressure. Energy consumption is lower for patients than for controls both during rest and during stress. Patients have an increased inotropic level which leads to high contractility and heart rate, but they still have the capacity to respond with further increases during stress, albeit not to the same degree that controls have. Patients with ASD have normal LV energy efficiency, in contrast to patients with heart failure due to ischaemic heart disease or dilated cardiomyopathy, indicating different causes of the decreased cardiac output. Further studies might illuminate if PV loop‐derived variables can provide prognostic information in patients with left‐to‐right shunts.Dr. Heiberg is the founder of Medviso AB, Lund, Sweden, the company that produces the Segment software. The remaining authors declare no conflict of interest.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.


In 1984, cardiologists and cardiac patients created an association offering physical activity (PA) for people with cardiovascular diseases in Luxembourg (0.6 million inhabitants). During the last 20 years, several associations created therapeutic PA for people with a wide range of non-communicable diseases (NCDs). Today more than 70 hours of therapeutic PA are weekly offered. Nevertheless, the organization of these PA is incomplete and not enough patients benefit from it.Sustainability of privately organized courses is challenging. Despite a governmental financial support, the organization of PA offer remains mainly based on the idealism of a limited number of volunteers. However, this kind of commitment is disappearing and jeopardizes a correct offer of therapeutic PA. Only a minority of physicians are referring their patients on a regular basis and only a minority of them are engaging in an active lifestyle.A project was launched in 2013 to compile, monitor and promote the therapeutic PA offered by different associations. As a result of this project, six associations created a sport federation in 2016 destined to improve the organization of therapeutic PA for people with NCDs. In 2018, the federation obtained an increase in the financial support from the Ministry of Health. The same year, a campaign promoted the therapeutic PA but had no impact on the number of patients counselled about therapeutic PA (26.6%) and on the physician's knowledge of the therapeutical PA offer (21%). The federation is now trying to develop and implement deeper actions, such as a PA referral scheme.The collaborative and synergetic work of the different associations offering PA for people with NCDs bundled their activities resulting in an increased consideration and support from the Ministry of Health. Nevertheless, structural improvements should be conducted to increase sustainably the number of physically active patients.The promotion and the organization of a valuable and sustainable therapeutic PA for patients with NCDs must be professionalized and publicly supported.A larger strategic vision needs to be developed by the government and healthcare providers to organize and support preventive medicine in Luxembourg.


Mitral valve disease, and in particular mitral regurgitation, is a common clinical entity. Until recently, surgical repair and replacement were the only therapeutic options available, leaving many patients untreated mostly due to excessive surgical risk. Over the last number of years, huge strides have been made regarding percutaneous, catheter-based solutions for mitral valve disease. Transcatheter repair procedures have most commonly been used, and in recent years there has been exponential growth in the number of devices available for transcatheter mitral valve replacement. Furthermore, the evolution of these devices has resulted in both smaller delivery systems and a shift towards transeptal access, negating the need for surgical incisions. In line with these advancements, and clinical trials demonstrating promising outcomes in carefully selected cases, recent guidelines have strengthened their recommendations for these devices. It is appropriate, therefore, to now review the current transcatheter repair and replacement devices available and the evidence for their use. Although the prevalence varies across countries, native mitral valve (MV) disease is the second most common valvular heart disease (VHD) in Europe ,2. MitraThe mitral valve is a complex anatomical structure whose function depends on an interplay between the left atrium, the valve leaflets, the subvalvular apparatus including chordae tendineae, papillary muscles, and the left ventricle. Complete imaging assessment of the MV is fundamental to plan and perform transcatheter repair and replacement procedures. Imaging assessment should focus on defining the severity and aetiology of the MV disease and a full morphological assessment of the valve, annulus, and subvalvular structures, left ventricular function and the spatial relationship between the MV and the coronary sinus (CS), left circumflex artery, left ventricular outflow tract, and the aortic valve. As such, echocardiography and multidectector computed tomography (MDCT) play an important role in patient selection, procedure planning, and device selection.Echocardiography is the mainstay when assessing MV disease, and current guideline recommendations are based on echo parameters ,4. The mMDCT has become increasingly important in the pre procedural assessment of patients undergoing many mitral valve repair procedures (particularly those targeting the MV annulus) and in TMVR where its use is mandatory prior to patient acceptance for many available devices . MDCT reTranscatheter mitral valve repair (TMRr) techniques can be broadly classified into three groups: devices aimed at modifying the MV annulus, devices targeting the MV leaflets, and devices targeting the subvalvular apparatus, specifically the chordae tendineae. The aim of all these therapies is to reduce MR by increasing leaflet coaptation. A summary of devices available is provided in ® mitral contour system™  and the ARTO™ system ).Devices aimed at modifying the MV annulus, reducing its dimensions, and thereby improving leaflet coaptation are used in secondary MR with annular dilatation. Annular modification can be performed directly  and the Millipede Mitral Annuloplasty System ) or indirectly via the coronary sinus  is a transfemoral, transeptal system with Conformité Européne (CE) approval delivered with a steerable catheter via a 25Fr sheath. The device is a polyester sleeve with radiopaque markers spaced at 8 mm intervals containing a contraction wire connected to an adjusting spool, which facilitates ‘cinching’ of the device to reduce the annular dimensions. The anchors are implanted along the posterior annulus beginning at the anterolateral commissure and continuing to the posteromedial commissure. Pre procedural CT and intraprocedural coronary angiography can be used to demarcate the trajectory of the circumflex artery to avoid injury. One-year outcomes on 60 patients following Cardioband™ implantation have been reported with modification of the device following the first ten patients to solve the problem of anchor disengagement . OverallThe Millipede IRIS Mitral Annuloplasty System™  is a transfemoral, transeptal system delivered through a 24 Fr deflectable catheter. The device is a semi-rigid complete nitinol ring with a zig-zag configuration and 8 helical stainless-steel anchors at its base. The anchors attach directly to the annulus and rotate independently such that they can be ‘unscrewed’ and replaced if initial placement is not satisfactory. Once the anchors are placed, tension is applied to draw the anchors together and modify the annulus. Rogers et al. reported the outcomes in seven patients implanted with the Millipede IRIS™ with no device related death, stroke, or myocardial infarction (MI) and ≤1+ MR at 30 days in all patients . The dev® mitral contour system™  utilizes the coronary sinus (CS) to modify the mitral valve annulus accessed through the internal jugular vein using a 10 Fr system. A sizing catheter determines the length of the CS and device length required (60 or 80 mm). The device consists of two nitinol anchors: one placed distally in the great cardiac vein and the other placed proximally in the coronary sinus with a nitinol connector ribbon. Deployment of the anchors is followed by cinching, which modifies the annulus.CarillonInitial observational studies demonstrated a good effect on MR reduction; however, many patients were unsuitable for device implantation due to risk of coronary compromise or insufficient MR reduction ,15. Folln = 87) or sham control (n = 33) [p = 0.049) as was improvement in 6-minute walk test distance and NYHA class. Lipiecki et al. reported long term results from a single centre with 6-year Kaplan–Meier estimate for mortality of 40% [The REDUCE FMR trial was a blinded randomized sham-controlled trial including 120 patients randomized on a 3:1 basis to either the Carillon device ((n = 33) . The devy of 40% . Better 2 to 17.6 mm2, p = 0.0034) and MR grade was ≤2+ in 85.7% and 90.5% at 1 and 12 months, respectively.The ARTO™ system  modifies the MV annulus using a bridge suture between a T-bar shaped anchor placed in the great cardiac vein (GCV) and a second anchor in the interatrial septum . DeploymTranscatheter edge-to-edge repair (TEER) devices are the most commonly used transcatheter mitral interventional devices  and emplThe MitraClip™  is a transcatheter, transeptal mitral valve repair system (TMVr). The current G4 iteration differs from its predecessors by having an expanded repertoire of device sizes  and independent leaflet grasping to allow optimization. The system consists of a 24 Fr steerable guide catheter and a clip delivery system. After transeptal crossing, the steerable catheter and clip delivery system allow orientation of the clip above and perpendicular to the leaflets. The opened clip is then passed into the ventricle and the leaflets are grasped as the clip is slowly pulled back towards the atrium. Once appropriate reduction in MR is confirmed without significant stenosis or interference with the other valvular structures, the device is released.The MitraClip™ device is the most widely studied of the TEER devices. The EVEREST I trial demonstrated device feasibility and safety with sustained reduction in MR to ≤2+ at 6 months . EVERESTp < 0.001) and reduced all-cause mortality at 24 months  or heart failure hospitalization . Further analysis of these two trials demonstrated a number of differences in the included cohorts [Controversy regarding this device arose with the simultaneous publication of two randomized controlled trials; COAPT  and MITR cohorts . Specifi cohorts  suggest It is important to note that all of these aforementioned studies were performed with older versions of the MitraClip™, and the current iteration (G4) has a number of improvements including an expanded range of sizes, continuous LA pressure monitoring, and individual leaflet grasping for optimizing results. A study including 59 patients treated with the G4 MitraClip™ demonstrated reduction in MR to ≤2+ occurred in 96.6% during the procedure and was sustained at 30-day follow up [The PASCAL™  repair system also employs a mitral valve edge-to-edge repair technique. Two systems are available, the PASCAL™ and the PASCAL Ace™, and they differ in device width . The system consists of a steerable sheath and implant catheter and offers increased range of movement to facilitate device placement in difficult anatomies. The system has three main components: the paddles and clasps between which the mitral valve leaflets are grasped, and a central spacer which acts to reduce the EROA without applying excessive leaflet tension. Independent leaflet clasping is also a feature of these devices.n = 36) as was transvalvular gradient.The prospective, single arm CLASP study enrolled 124 patients with both functional (69%) and degenerative 31%) severe MR. Successful implantation was achieved in 96% of patients. At 2 years, the major adverse event rate was 16.9% with 80.3% survival [% severe Current guidelines do not specify a preferred TEER device for TMVr and there are currently no randomized studies comparing the two. However, the CLASP IID/IIF randomized controlled trial comparing both devices is currently recruiting NCT03706833.A number of devices target the subvalvular apparatus and aim to restore the tethering function of the chordae tendineae.The NeoChord™  artificial chordae delivery system uses an expanded polytetrafluoroethylene (ePTFE) suture to create a new chordae tendineae. It has CE approval for the treatment of MR due to prolapse or flail leaflet. The device consists of a handheld delivery device, a cartridge into which the suture is loaded, a needle, and a leaflet capture verification monitor. The procedure is transapical, requiring a lateral mini-thoracotomy. TEE guides the incision site in the LV apex to attain proper alignment with the mitral valve, and the instrument is introduced. Leaflet grasping is confirmed on the verification device, and the suture is deployed. Several sutures can be inserted, each one individually secured to a pledget on the epicardial surface of the heart.The TACT study examined the feasibility, safety, and efficacy of the NeoChord system. From 30 patients with severe MR due to MV prolapse (Carpentier type II), 86.7% of patients had a reduction in MR to ≤2+ . Major aThe HARPOON™ beating heart mitral valve repair system  is a chordal system using an ePTFE suture delivered transapically via a 14 Fr introductory system. The device is positioned beneath the posterior MV leaflet, and the needle passes through the target scallop, creating a knot on the atrial surface. The suture is then withdrawn through the device, tightened, and fixed to a pledget on the epicardial surface of the ventricle. The combined results of two multicentre studies were reported by Gammie et al., including 65 patients . The pri2), broad or commissural MR jets, flail leaflet, and Barlow’s disease, all of which are unsuitable for edge-to-edge repair, may be more appropriate for TMVR [TMVR techniques have increased in frequency in recent years as have the number of devices now available for use. TMVR continues to be reserved for inoperable or high surgical risk patients, and current guidelines have highlighted the paucity of trial data concerning their use . Howeverfor TMVR . Until rfor TMVR ,37,38,39for TMVR . While Vfor TMVR ,39, ViR for TMVR , highligDedicated TMVR devices, previously only delivered through the transapical route, have evolved significantly with transeptal devices now showing promise. Furthermore, greater standardization of pre-procedural imaging for planning and predicting potential complications has led to improved patient selection; however, there continues to be a large number of patients not suitable to undergo these procedures. A review of 40 patients by Coisne et al. screened for potential TMVR deemed 60% to be unsuitable due to anatomical reasons and risk of LVOTO . This hi2 measured using a device-specific virtual valve implantation on MDCT predicts LVOT obstruction with a high sensitivity and specificity [https://clinicaltrials.gov/ (accessed on 1 December 2021) are outlined in LVOTO remains one of the biggest concerns with TMVR. Obstruction of the “neo-LVOT” can be from prosthesis protrusion into the LVOT or from displacement of the anterior MV leaflet. Valve-in-MAC procedures are at particular risk. An estimated neo-LVOT area of ≤1.7 cmcificity . A numbecificity  or intencificity . Hybrid Tendyne™  is a transapical system consisting of two stents. The inner nitinol stent houses the valve leaflets (three leaflets of bovine pericardium) while the outer stent is D-shaped to conform to the native MV. The straight part of the D-shape is orientated towards the aortomitral continuity. The stents are connected with a polyethylene terephthalate (PET) fabric cuff that provides sealing and prevents perivalvular leak. Valve deployment begins in the left atrium and is guided by TEE. The valve is fully repositionable and retrievable during the procedure to optimize the results. Tethering to the LV is via a braided fibre secured to a pad on the epicardial surface of the ventricle.Two-year data has been published for patients with both primary and secondary MR ,45. TechIntrepid™  is now available as both a transapical and transeptal system. It has a two-stent design. The inner stent houses the trileaflet bovine pericardial valve and the outer stent forms a fixation ring. The valve itself measures 27 mm and the fixation ring is available in variable sizes. Fixation and sealing are achieved in multiple ways: oversizing (10–30%) to provide radial force, conformation of the flexible atrial portion of the fixation ring to the MV annulus, the “champagne cork” (narrow neck and wider body) formation between the atrial and ventricular portions, which avoids apical displacement during systole, and three rows of friction elements that further aid fixation. The two-stent design ensures that the inner stent housing the valve leaflets maintains the same circular conformation during both systole and diastole.The results of 50 patients of high or extremely high surgical risk patients treated using the transapical device were reported in 2018 . One patTiara™  is a transapical self-expanding nitinol valve with three bovine pericardial leaflets. The valve has a D-shaped configuration designed to fit MV anatomy. Ventricular anchoring structures secure the valve onto the fibrous trigones and the posterior shelf of the MV annulus. Delivery is via a 32 Fr sheath through the apex into the left atrium. The atrial portion of the device is unsheathed, orientated, and retracted into position. The ventricular portion is then released, and the valve is anchored. Plans to develop a transfemoral/transeptal deliver system were recently put on hold. An early feasibility study (TIARA-I) and extended clinical study (TIARA-II) are currently underway, and pooled preliminary results of 71 patients demonstrated no procedural deaths and 93% successful deployment . Thirty-The EVOQUE™  TMVR is a transeptal system consisting of a self-expanding nitinol frame with a bovine pericardial valve delivered via a 28 Fr sheath. The delivery capsule is aligned using TEE and passed through the mitral valve where unsheathing begins in the ventricle. As the valve is unsheathed, it is anchored by capturing the valve leaflets and subvalvular apparatus. The atrial portion of the valve has a sealing skirt to prevent PVL. Initial results for fourteen patients demonstrated technical success in 92.9% (13 of 14 patients) . One reqThe HighLife™ TMVR  system consists of two components: a 31 mm ring-shaped subannular implant (SAI) that encircles the subvalvular apparatus and is delivered through an 18 Fr catheter retrogradely via the femoral artery and aortic valve, and secondly the valve component, delivered transeptally through a 39 Fr catheter that sits within the subvalvular ring. The SAI is made of nitinol, covered with PET while the valve is self-expanding nitinol with bovine pericardium. Of 30 patients implanted with HighLife technical success was reported in 27 (90%) . Four maThe Sapien M3™  device utilizes a Sapien 3  valve and adds a subvalvular PET nitinol ‘dock’ that encircles the chordae tendineae and acts as an anchor for the prosthetic valve when it is deployed. The system is delivered transeptally  via a 20 Fr system. The valve component of the system is identical to the Sapien 3 29 mm valve. The subvalvular ‘dock’ can be recaptured if necessary. The results of ten patients were reported by Webb et al. . SuccessThe Cardiovalve™  transeptal system consists of two frames: atrial and ventricular. The valve has bovine pericardial leaflets, and the frame is designed to mirror modern day surgical mitral valve prosthesis with a low profile on both the atrial and ventricular portions. The 30 Fr system is delivered transeptally, and implantation occurs in three steps. On crossing the valve, the leaflets are grasped, and once adequate grasping and co-axial alignment has been confirmed, the atrial flange  is released and finally the ventricular frame is released. Three valve sizes are available. Results from five patients demonstrated 100% successful implantation with no residual MR. At 30-days, three deaths occurred (60%) with two related to bleeding events .The Cephea™ TMVI system  is a self-expanding nitinol valve with a double disc structure and bovine pericardial leaflets. The atrial disc is positioned at the floor of the left atrium and a central column provides support and houses the pericardial leaflets. The ventricular disc then anchors to the subvalvular apparatus. One size (36 mm) is currently available. Outcomes for three patients with primary degenerative MR have been reported . SuccessThe AltaValve™  is a novel supra-annular, atrial fixation only device delivered via the transeptal route. The device is a self-expanding nitinol spherical frame available in sizes ranging from 50–95 mm to accommodate varying LA anatomies. The nitinol sphere contains the trileaflet bovine pericardial valve that is available in one size (27 mm). There is no active fixation of the valve, and anchoring is achieved by oversizing of the LA sphere (by 10–30%) and the annular portion of the valve (by 5–20%). The upper portion of the sphere has a large open cell structure. A PET skirt on the lower portion of the valve allows rapid endothelialization and prevents PVL. The transeptal system requires a 32 Fr transeptal sheath. A small number of cases using the AltaValve™ transapically have been reported, and one case of transeptal deployment was reported in 2019 with successful implantation and no significant residual MR . SuccessThe prevalence of mitral regurgitation, particularly due to degenerative MV disease, is set to continue to increase in parallel with our ageing population. Transcatheter mitral valve therapies are therefore likely to expand. A number of engineering challenges, particularly in the TMVR sphere, must be overcome, including smaller delivery systems, improved sealing mechanisms to avoid paravalvular leak, and reduced device and AMVL encroachment in the LVOT to minimize the risk of LVOTO. Ancillary technologies and procedures aimed at preventing LVOTO such as septal reduction and therapies directed at the AMVL are also likely to increase in frequency, and operators will need to become proficient in these to provide reproducible results for patients. ViMAC and ViV present a number of challenges, and the results of currently recruiting and planned studies will inform much of the treatment of these entities going forward. While at present transcatheter MV therapies for the management of MR remain reserved for those patients unable to undergo surgical procedures, much like the evolution of transcatheter aortic valve replacement, it is probable that with advanced device iterations many of the current technical difficulties to the percutaneous treatment of MR will be overcome, and with appropriate clinical trial data, expansion of these therapies to lower risk groups could be on the horizon.Transcatheter MV interventions have increased exponentially over the last number of years. Transcatheter repair devices, particularly TEER devices, have heretofore been most commonly used, and with appropriate patient selection, have good outcomes. However, not all patients are suitable for repair procedures, and TMVR is increasingly becoming a viable option for patients with high surgical risk and prohibitive anatomy for transcatheter repair. Although data remains scarce, a large number of prospective studies are planned in this space in the coming months and years. In parallel, engineering of currently available devices continues to evolve such that many of these devices are already on their second or third iteration and have gone from transapical to transeptal delivery systems. Given the significant morbidity associated with mitral valve disease, these advances are to be welcomed and will broaden treatment options available to these patients.


Failing Fontan patients present a unique challenge for mechanical circulatory support. We report on a 17-year-old patient with Fontan failure and preserved ventricular function who underwent mechanical cavopulmonary support using a novel cannulation technique. The failure of a Fontan circulation often leads to venous and lymphatic congestion, ascites and protein-losing enteropathy (PLE). The failure of a Fontan circulation often leads to venous and lymphatic congestion, ascites and protein-losing enteropathy (PLE). Preserved ventricular function in failing Fontan patients is an independent risk factor for mortality after heart transplantation. These patients have higher PVR, higher central venous pressures and more structural liver changes .et al. [In this subset of patients, cavopulmonary support is required to improve organ function. This concept was first successfully described by Prêtre et al.  who tookThe data underlying this article are available in the article.The institutional review board approved this study (code 21-0409).® ventricular assist device in the cavopulmonary circulation as a bridge to candidacy.We report on a 17-year-old man with double-inlet left ventricle and pulmonary stenosis. He had undergone placement of an aorto-pulmonary shunt, partial cavopulmonary connection, thrombectomy of the left pulmonary artery with patch enlargement and extracardiac total cavopulmonary connection with an 18-mm Goretex conduit at the age of 19 months to complete the Fontan palliation. In addition, he had multiple interventions to stent the pulmonary arteries and to fenestrate the Fontan circulation. Nevertheless, he developed PLE and was listed for heart transplantation. He deteriorated clinically, and his functional status gradually disqualified him for heart transplantation. Therefore, we decided to implant a Berlin Heart EXCORHaemodynamic parameters before the procedure were as follows: central venous pressure 20 mmHg, left atrial pressure 10 mmHg and transpulmonary gradient 10 mmHg. The arterial oxygen saturation was 85% with a right-to-left-shunt over the fenestration. The function of the left ventricle was normal. Abdominal sonography showed ascites, enlarged liver veins and liver fibrosis.® ventricle (50 ml). Cardiopulmonary bypass time was 180 min. The patient was extubated on postoperative day 2. The PLE symptoms and renal function had improved after 1 month and he was relisted for heart transplant 3 months after VAD implantation. Heart transplant was performed 4.5 months after VAD implantation. He was discharged from the hospital in good clinical condition after a long recovery process 5 months after heart transplant.As he had 5 previous sternotomies and extensive adhesions were expected, it was decided to cannulate the femoral vessels and the internal jugular vein for full cardiopulmonary bypass without the need for extensive surgical dissection and central cannulation. On pump beating heart, the partial cavopulmonary connection was taken down, and the Fontan fenestration was closed by direct suture. The resulting defect on the right pulmonary artery was repaired with a bovine pericardial patch. The 18-mm total cavopulmonary connection conduit was divided and the superior part was anastomosed to the Goretex graft extension (18 mm) of the VAD outflow cannula. The inferior part was anastomosed to the Goretex graft extension (20 mm) of the inferior part of the novel venous cannula (inflow). The SVC was anastomosed to a 16-mm Goretex graft extension of the superior part of the venous cannula inflow, . The canet al. [et al. [® pump. With this type of support, we hope to be able to improve outcomes after heart transplantation for Fontan patients by recovering the function of their secondary organs before transplant.The implantation of a pulsatile sub-pulmonary assist device in failing Fontan patients with a preserved ejection fraction of the systemic ventricle has been described previously by Prêtre et al.  and Moos [et al. . The con


Imaging phantoms are used to calibrate and validate the performance of magneticresonance imaging (MRI) systems. Many new materials have been developed foradditive manufacturing  processes that may beuseful in the direct printing or casting of dimensionally accurate, anatomicallyaccurate, patient-specific, and/or biomimetic MRI phantoms. The T1, T2, and T2*spin relaxation times of polymer samples were tested to discover materials foruse as tissue mimics and structures in MRI phantoms. This study included acohort of polymer compounds that was tested in cured form. The cohort consistedof 101 standardized polymer samples fabricated from: two-part silicones andpolyurethanes used in commercial casting processes; one-part optically curedpolyurethanes used in 3D printing; and fused deposition thermoplastics used in3D printing. The testing was performed at 3 T using inversion recovery, spinecho, and gradient echo sequences for T1, T2, and T2*, respectively. T1, T2, andT2* values were plotted with error bars to allow the reader to assess how well apolymer matches a tissue for a specific application. A correlation was performedbetween T1, T2, T2* values and material density, elongation, tensile strength,and hardness. Two silicones, SI_XP-643 and SI_P-45, may be usable mimics forreported liver values; one silicone, SI_XP-643, may be a useful mimic formuscle; one silicone, SI_XP-738, may be a useful mimic for white matter; andfour silicones, SI_P-15, SI_GI-1000, SI_GI-1040, and SI_GI-1110, may be usablemimics for spinal cord. Elongation correlated to T2 (p = 0.0007), tensilestrength correlated to T1 (p = 0.002), T2 (p = 0.0003), and T2* (p = 0.003). The80 samples not providing measurable signal with T1, T2, T2* relaxation valuestoo short to measure with the standard sequences, may be useful forMRI-invisible fixturing and medical devices at 3 T. The B1 pulse,for which the frequency is at or near the precessional frequency of the nuclear spinbeing imaging, is generated from transverse-mounted RF coils. Most often, MRIdetects the induced field produced by precessing proton spins on water and fat witha resonant frequency z direction). The proton spin magnetization,1, T2,and T2*, of different materials and tissues.1 The MRI signal can be sensitive to several other materialparameters, such as proton density, diffusion, electrical conductivity, andmagnetic susceptibility, depending on the type of pulse sequence used. Inthis paper, we are only focusing on spin relaxation times.Magnetic resonance imaging (MRI) has become an invaluable medical diagnostic tool inmany applications -4. MRI ihe field . Typical1 is the longitudinal relaxation time, which characterizes the time ittakes to go from the initial excited z-axis magnetization,z-axis magnetization, T2 is the transverse relaxation time and characterizes the decay of thetransverse magnetizationT2* is thetotal dephasing time that includes effects due to intrinsic material properties(T2 relaxation) plus extrinsic field inhomogeneities due to sample orscanner created field inhomogeneities. From an operational perspective,T2 describes the dephasing component that cannot be rephased by aspin echo sequence that incorporates rephasing pulses. T2* is always lessthan T2 and is a function of the nonlocal environment. SinceT1 relaxation involves energy lost to adjacent macromolecules(spin-lattice), and T2 decay involves angular momentum transfer toadjacent spins (spin-spin), there may be material properties such as density,elongation, tensile strength, or hardness that correlate with T1,T2, and T2* values, as they are sensitive to molecularstructure and interactions [where ractions .MRI calibration phantoms are used to assess stability in MRI scans over time, as wellas establish consistency between manufacturers and models of scanners. Thesephantoms generally include accurately located vials of specific chemical solutions, 7. The In previous research, small numbers of two-part silicone and polyurethane polymershave been imaged with computed tomography (CT), MRI, and ultrasound , 23. The1,T2, and T2* relaxation values similar to human tissues foruse as mimics, or, materials with no measurable relaxation values for use asMRI-compatible support structures. This study did not investigate thematerial’s dielectric or magnetic susceptibility properties, which can alsoinfluence the MRI signal by distorting the RF and magnetic fields.This research was performed to discover or predict materials with T21,T2, and T2* at 3 T were obtained from peer-reviewedjournal papers. The selection criteria for sample fabrication included availabilitywithin the project schedule, cost within available funding, ease and speed offabrication, and toxicity that could be accommodated with standard protective gearand large room ventilation.A list of the physical properties of candidate materials was compiled frommanufacturer data sheets. The documented tissue values for Twww.formlabs.com) Form 2 stereolithographic laser (SLA)printer.2 Certain commercial equipment, instruments, and/or materialsare identified in this report in order to adequately specify theexperimental procedure. Such identification does not imply recommendation orendorsement by the National Institute of Standards and Technology, nor doesit imply that the equipment and/or materials used are necessarily the bestavailable for the purpose. Standard samples of one-partpolyurethanes and fused deposition modeling (FDM) materials were procured fromthird-party 3D printing fabricators Protocam  (www.protocam.com), Protogenic  (www.tenere.com), Protolabs  (www.protolabs.com), and Sculpteo  (www.sculpteo.com). Since printer manufacturers offer materialsoptimized for each printer model and offer some compatibility with third-partymaterials, this sourcing strategy gave access to materials and chemistries from allmajor suppliers .Samples of 3D printing materials were fabricated as 10 mm × 15 mm × 20mm (± 0.01 mm) cuboids. Standard samples of one-part ultraviolet-curedpolyurethanes were printed with a FormLabs  (www.silicones-inc.com), and from Smooth-On, Inc. (www.smooth-on.com). A sample of a two-part polyurethane fromHuntsman  . Since T1 and T2 are intrinsic characteristicsof materials and tissues, the exact dimensions of the samples were not relevant,provided enough protons were captured to emit a signal measurably above the scannernoise floor. T2* measurements are affected by the sample geometry, sincemagnetic susceptibility variations can lead to additional field inhomogeneity. Careneeds to be taken when associating T2* values with material properties,particularly for materials with longer T2* times, where the spindephasing may be dominated by system and geometry inhomogeneities.Samples of cured silicones were cut down to 20 mm × 25 mm × 5 mm(± 2 mm) from precast material obtained from Silicones, Inc. (www.amazon.com), which exhibited no MRI signal at 3 T with the sequencesused for testing. An Agilent 7T310  (www.agilent.com) preclinicalscanner operating at 3 T was used for the measurement of T1,T2, and T2* in this study. The scanner was equipped with a140 mm quadrature birdcage RF coil from Doty Scientific  (www.dotynmr.com) with an isocenter accommodating 12 samples withinthe uniform field of view. To maintain coil loading between groups, one pill well ineach group of 12 samples was filled with deionized (DI) water. The scanner used forthis study was kept at a high level of calibration for quantitative imaging phantomdevelopment at the National Institute of Standards and Technology (NIST).The test samples were placed in a 31 day commercial pill organizer  slice. The RF coilwas retuned and matched at 50 ohms for the imaging of each section to accommodatethe variable loading of samples.The MRI sequences listed in 1, T2, and T2* relaxation times of the sampleswere obtained from series of magnitude images obtained from conventional inversionrecovery, spin echo, and gradient echo sequences, respectively [1, the inversiontime, TI, was varied, and for T2 and T2*, the echo time, TE,was varied. The relaxation times were computed using the Python-based NISTPhantomViewer software application (www.github.com/NIST/PhantomViewer) by fitting the observed signal,1 and Eq. (4) for T2 and T2*. Standardnonlinear least squares fit routines (Levenberg Marquardt) from the Scipy library(www.scipy.org/scipylib) were used.The Tectively . The inv1guess = TIamin/ln2 for T1 andT2guess = 200 ms for T2 fitting, where TIaminis the value of TI that gives a minimum signal. The computed relaxation values anderror bars were plotted alongside tissue relaxation values and error bars taken fromliterature.The initial parameter guesses for the nonlinear least squares fitting wereT1, T2, andT2* values were plotted against the physical properties listed by themanufacturers, in addition to a least squares statistical analysis performed usingthe JMP  (www.jmp.com) software application. Materials withR2 > 0.5 and p < 0.05 wereconsidered statistically significant for the purposes of this exploratory study.To uncover predictive relationships, the measured T3et al. [1 and, T2 values for tissues found in literature areprovided in The properties of over 1200 castable and printable materials were reviewed for use asmimics for human tissues. Many of the human tissue values are cited by the originalsources in this study -43 and aet al. . TheT1 1, T2,T2* values too short to measure using standard pulse sequences, areprovided in Materials with signals below the noise level and T1, T2, and T2* values of the samples that hadmeasurable values are listed in 1 value, along with their respectivephysical properties. The samples exhibiting measurable signal are shown in a photoof the tray in The T1, T2, and T2* values of the materials andvalues of human tissue are plotted in The T1 vs. T2, T1 vs. T2*, andT2 vs. T2* values are plotted in The TR2, pvalues, and fit model. Elongation correlated to T2 (p =0.0007), and tensile strength correlated to T1 (p =0.002), T2 (p = 0.0003), and T2*(p = 0.003). Density and hardness did not correlate torelaxation values.A summary of the statistical analysis is provided in 41 and T2values were near tissue values. The materials with measurable T1,T2, and T2* values using the available MRI sequences werecast silicones, although T1, T2, and T2* were notpredicted by silicone condensation or addition cure chemistry. The statisticalanalysis showed that T2 increased with increasing material elongation,suggesting that increased molecular distance reduced the opportunity for spin-spinenergy transfer. The other significant correlation was that T1,T2, and T2* decreased with increasing tensile strength,suggesting that increasing molecular rigidity increased spin-lattice and spin-spincoupling. T1, T2, and T2* were not predicted bydensity or hardness.There were several materials for which the measured T2*tissues. These low-signal materials might be used in the fabrication of very preciseMRI-compatible fixtures and accessories such as RF and gradient coil housings,magnetic probe holders, patient head and body alignment fixtures, or functional MRIactuators to name a few examples.The relaxation values for the 3D printed thermoplastics and polyurethanes were notmeasurable with the scanner and sequences used in the study due to short decaytimes. Future research will be conducted on a scanner capable of running ultrashort(UTE) sequences to determine if the “no signal” and “nofit” samples from this research have use as mimics for short T1, T2, and T2* forthe same tissue because most papers focused on one or two of the three relaxationtimes due to lack of instrumentation. The intimate details of each material’schemistry and processing were not known, so the size and mobility of the moleculeswere not known. Future chemistry knowledge might explain some apparent groupings inthe density plots and justify separate fits in future analyses.The study was limited by several factors. Only the four material characteristicsevaluated in this study were consistently reported by all manufacturers. Fewpeer-reviewed papers reported T1,T2, and T2* relaxation times change with field strength,it is expected that the relative material/tissue values would be different at 1.5 Tand 7 T.Given this study was performed at 3 T and that tissue and material T51 = 831.3 ms, T2 = 26.9 ms) andSI_P-45 , may be usable mimicsfor reported liver values; one silicone, SI_XP-643 , may be a useful mimic for muscle; one silicone,SI_XP-738 , may be a useful mimicfor white matter; and four silicones, SI_P-15 , SI_GI-1000 , SI_GI-1040 , andSI_GI-1110 , may be usable mimicsfor spinal cord [2(p = 0.0007), and tensile strength correlated to T1(p = 0.002), T2 (p = 0.0003), andT2* (p = 0.003). The 80 samples not providingmeasurable T1, T2, and T2* relaxation times withthe standard sequences used in this study should be good candidates forMRI-compatible fixtures and medical devices at 3 T.Two silicones, SI_XP-643 (Tnal cord , 42. Elo


It is commonly known that Down syndrome (DS) and congenital cardiovascular abnormalities go hand in hand. Most frequently, complete atrioventricular septal abnormalities have been linked to DS. Along with DS, ventricular septal defect (VSD), atrial septal defect, tetralogy of Fallot, and patent ductus arteriosus have also been reported. We present a case of DS with VSD who underwent VSD correction. Echocardiography prompted the diagnosis, which was then confirmed by surgery. The patient was successfully transferred out of the hospital. After correcting the VSD, the survival and quality of life of the DS patient have improved. The range of congenital cardiac defects in Down syndrome (DS) patients varies. A heart abnormality affects roughly 30% of babies with trisomy 21 who also have cardiac malformation. Congenital heart disease, also known as a congenital heart defect, refers to a several anatomical issues with the heart or its major blood arteries that exist from birth. About 14-16% of all congenital cardiovascular problems are ventricular septal defects (VSDs). Congenital cardiovascular defects, the most typical birth defect, affect around eight of every 100 newborns per year, or 1% of live births. It is the leading cause of birth defect-related mortality in the first year of life. There are many clinical signs and symptoms of DS, and they can affect every system of the body. The most serious ones include congenital vascular malformation, low stature, heart disease, gastric illness, orthopedic deformities, and intellectual disability. Undoubtedly, heart disease is the primary cause of good or bad outcomes in these children. Pulmonary arterial hypertension (PAH) may manifest sooner and progress more violently in patients with DS. There are few effective treatments for Eisenmenger syndrome, such as the use of vasodilators and systemic arterial to pulmonary shunts surgically placed to increase oxygen saturation, and the chance for fatality is exceptionally high in this group of patients. The three main fatalities in patients with DS and cardiac illness are cardiac arrest, infections, and pulmonary edema. This last step causes a survival rate drop of up to 58% and manifests early in individuals with atrioventricular septal defect (AVSD). In DS, upper airway obstruction is expected to occur 30-50% of the time. Individuals with DS have an increased risk of infection, particularly respiratory tract infections, which are more prevalent in this group. A prevalent cause of death, bronchopneumonia, has a mortality rate 124 times higher than the overall population [A four-month-old hospitalized boy showed facial dysmorphism, upward slanting of the palpebral fissure, a flat nasal bridge, and a protruding tongue. He also had small, wide hands and a flat occiput which are some of the signs of DS Figure .2 monitoring. Next, a 24 g intravenous (IV) line was secured, the patient was connected to an electrocardiogram (ECG), and was induced using an injection of midazolam 0.05 mg/kg, fentanyl 2 µg/kg, and vecuronium 0.1 mg/kg. The airway was then secured with 4.0 uncuffed endotracheal tube after bilateral equal air entry. Ventilation was maintained at a rate of 32 breaths per minute, a total volume of 20 mL, an I:E ratio of 1:2, and FiO2 of 60%. Vecuronium top-ups and sevoflurane were used to maintain the patient. For invasive blood pressure monitoring, femoral arterial catheterization was performed. Heparin 300 IU was administered intravenously after the sternotomy. The clamp on the venous line was released, and cardiopulmonary bypass (CPB) was started when the activated clotting time was more than 420 seconds. Sevoflurane, IV fluids, and ventilation were stopped after appropriate flows, and venous drainage was in place. To stop movement, muscle relaxants were provided again. Anesthesia was maintained by utilizing IV or inhalational medications delivered via a vaporizer in the circuit’s fresh gas line. VSD was sealed using a polytetrafluoroethylene patch , left-to-right shunt, dilated left atrium (LA) and left ventricle (LV), and severe PAH. The renal function test, liver function test, and complete blood count were all within normal ranges. On the day of the surgery, after written informed consent from the parent and postoperative intensive care unit (ICU) stay, the patient was wheeled to the operating room and placed under the inhalational agent sevoflurane, with SpOFor the discontinuation of CPB, the arterial blood was warmed to 32°C. Arterial blood gas was taken during rewarming for blood gas analysis. Injection protamine ensured enough anticoagulation during rewarming, and dissociation from CPB and activated clotting time confirmed it. Maintaining sufficient analgesia, amnesia, and neuromuscular blockade are significant anesthetic concerns during rewarming. It is possible to provide more opioids, benzodiazepines, and relaxants. Nitroglycerin pop-ups are given to regulate blood pressure and aid in rewarming if the mean arterial pressure is raised. To prevent air embolism into the cerebral or coronary circulations following operations where the heart was opened, de-airing maneuvers were performed under transesophageal echocardiography supervision. The venous return lines will be clamped in conjunction with positive-pressure ventilation to force air from the pulmonary veins forward. The removal of the aortic cross-clamp restores coronary perfusion. Once the skin closure was begun, injection Neomol 15 mg/kg IV was given with injection Emeset 0.1 mg/kg. Once the surgery was done and the patient was on adequate spontaneous ventilation, the reversal was achieved with injection myopyrolate (0.05 mg/kg) injected slowly. The patient was fully awake, conscious, extubated, and shifted to the ICU.DS, or trisomy 21, was first identified in 1866 and is a genetic disorder. Overall, 95% of cases are primary trisomies, while the remaining 5% are translocation and mosaic variants. One in 650 live births is the frequency of presentation. About 1% of the population experiences this frequency. Cardiac abnormality is the leading cause of mortality during the first two years of life. The survival chances of DS patients are 72% lower due to congenital cardiac abnormalities. Higher success rates than AVSD are seen in the early stages of ASD and VSD. Nevertheless, research from the last 20 years revealed that survival rates for newborns with DS and a healthy heart improved from 93% to 97% and from 78% to 90%, respectively. The pulmonary vascular resistance of children with congenital cardiac disease and DS is exceptionally high, and they are more likely to experience early pulmonary vascular bed injury. Atrioventricular valve regurgitation and the evolution of pulmonary vascular disease make the first six months of life the optimal period for some repairs. Some DS patients have undergone successful surgeries as late as their second year, while others succumb to a pulmonary hypertensive crisis as early as in the first six months . The sizImprovements in critical care facilities, the use of vasodilators, and successful management of early congenital heart defect repair to prevent sepsis, prognosis, and anesthetic considerations were successfully managed, all of which contributed to the patient’s ability to live longer with a higher quality of life


Autonomic alterations in blood pressure are primarily a result of arterial baroreflex modulation of systemic vascular resistance and cardiac output on a beat-by-beat basis. The combined central and peripheral control by the baroreflex likely acts to maintain efficient energy transfer from the heart to the systemic vasculature; termed ventricular-vascular coupling. This level of control is maintained whether at rest or during exercise in healthy subjects. During heart failure, the ventricular-vascular relationship is uncoupled and baroreflex dysfunction is apparent. We investigated if baroreflex dysfunction in heart failure exacerbated ventricular-vascular uncoupling at rest, and during exercise in response to baroreceptor unloading by performing bilateral carotid occlusions in chronically instrumented conscious canines. We observed in healthy subjects that baroreceptor unloading caused significant increases in effective arterial elastance (Ea) at rest (1.2 ± 0.3 mmHg/ml) and during exercise (1.3 ± 0.2 mmHg/ml) that coincided with significant increases in stroke work (SW) (1.5 ± 0.2 mmHg/ml) and (1.6 ± 0.2 mmHg/ml) suggesting maintained ventricular-vascular coupling. Heart Failure significantly increased the effect of baroreceptor unloading on Ea at rest (3.1 ± 0.7 mmHg/ml) and during exercise (2.3 ± 0.5 mmHg/ml) whereas no significant increases in stroke work occurred, thus signifying further ventricular-vascular uncoupling. We believe that the enhanced ventricular-vascular uncoupling observed during baroreceptor unloading only worsens the already challenged orthostatic and exercise tolerance and thereby contributes to poor exercise performance and quality of life for heart failure patients. Beat by beat control of blood pressure is crucial to the maintenance of cardiovascular performance. The primary mechanism by which blood pressure control occurs is through arterial baroreflex mediated changes in sympathetic and parasympathetic activity to modify heart rate and vascular resistance which thereby maintains blood pressure within normal ranges in response to changes in posture, exercise, and activation of other cardiovascular reflexes or local vascular responses .In heart failure arterial baroreflex regulation is significantly altered. Most notably the ability of the baroreflex to increase blood pressure in response to a hypotensive stimulus is attenuated and this is primarily an effect of an attenuated ability to increase cardiac output due to depressed ventricular function . Furthera) vs. ventricular maximal elastance (EMAX). Ea is a vascular property that was originally derived by relating total peripheral resistance with systolic, and diastolic time periods, as well as the diastolic time decay constant to assess the load imposed by the vasculature on the left ventricle . This latter method showed limited bias and statistical difference from the fully derived method  adult mongrel canines 18–25 kg were selected based on their willingness to walk on a motor driven treadmill at 3.2 km/hr with no incline. We have shown previously that gender does not impact cardiovascular responses to activation of the muscle metaboreflex . FurtherAll anesthetic, analgesic and surgical procedures used in this study have been documented in previous studies . BrieflyIn the first surgery a left thoracotomy was performed by entering the 3-4th intercostal space. The pericardium was incised to access the apex of the heart for insertion of a telemetric pressure sensor  and place 0-Flexon steel pacing leads  on the epicardium for measures of ventricular pressure and induction of heart failure respectively. Additionally, the ascending section of the aorta was dissected from its surrounding tissue for placement of a 20 PAU flow probe  to measure cardiac output. The pericardium and ribs were reapproximated and the chest was closed in layers. All cables and wires were tunneled subcutaneously and exteriorized at the scapulae. Animals recovered for a minimum of 14 days prior to the next procedure.The second surgery was a left retroperitoneal approach to access the terminal aorta and renal artery. A fluid 19-gauge polyvinyl catheter  was placed into the most cranial lumbar artery branch of the terminal aorta for measures of systemic blood pressure. Additionally, a 10 PAU flow probe  and two hydraulic vascular occluders  were placed around the terminal aorta caudally to the catheter to measure and manipulate hindlimb blood flow for experiments unrelated to the current study. Lastly a 4 PSB flow probe  was placed around the left renal artery for experiments unrelated to the current study. The retroperitoneal space was closed in layers and all cables, catheters and occluder lines were tunneled and exteriorized at the scapulae. Animals recovered a minimum of 14 days prior to the next surgery.The final surgical procedure was performed using a single 4–5 cm vertical incision on the neck for placement of a vascular occluder  on each carotid artery caudally from the carotid body to be used for baroreceptor unloading. The neck incision was closed in layers and occluder lines were tunneled and exteriorized at the scapulae. Animals recovered for a minimum of 14 days prior to any experiments.Experiments were performed after a minimum of 14 days post-surgery. For each experiment animals were given 10–20 min to acclimatize to the laboratory environment. After acclimation all the fluid catheter was attached to a pressure transducer  and the flow probes were connected to their respective flow channels on a TS420 flowmeter . The telemetric DSI implant for the ventricular catheter was turned on to transmit data to the receiver . All data was collected and analyzed using Labscribe acquisition software . With the animals standing on the treadmill at rest the carotid vascular occluders were inflated for 2 min. The data were averaged over the last 1 minute of carotid occlusion. After a minimum of 20 min recovery at rest or on a separate day, the treadmill was started, and the speed raised to 3.2 km/h and maintained for at least 3–5 min to achieve steady state and the carotid occlusions were repeated. All experiments were repeated in the same animals after induction of heart failure induced via rapid ventricular pacing at 225 beats per minute for 31 ± 5 days. Thus, each animal was observed in every setting and condition: e.g., each animal served as its own control in this longitudinally designed study.Cardiac output, mean arterial pressure, and left ventricular pressure were measured and recorded continuously and all other variables shown in this study were derived from these waveforms or through calculations. Heart rate was derived from the left ventricular pressure wave form. Stroke Volume was determined by Cardiac Output/Heart Rate, Total Vascular Resistance was determined by Mean Arterial Pressure/Cardiac Output. End Systolic Pressure and rates of ventricular contractility were derived from the left ventricular pressure wave. Effective Arterial Elastance, the vascular component of the ventricular-vascular coupling relationship was calculated from two previously described methods. The first method is derived from the ventricle  End Sys  . The arta were significantly enhanced. By breaking these separate measures of elastance into their components we observe that the vascular component of the ventricular-vascular relationship is impacted by multiple factors. Effective Arterial Elastance PV was significantly increased because of significant albeit attenuated increase in End Systolic Pressure coupled with a significant reduction in Stroke Volume during bilateral carotid occlusion in both exercise and rest. Alternatively Effective Arterial Elastance Z was significantly increased during bilateral carotid occlusion at rest and during exercise because of the maintained increase in Total Vascular Resistance in heart failure coupled with the significantly enhanced heart rate. Together, the ventricular deficits coupled with the enhanced Effective Arterial Elastance significantly impairs energy transfer from the left ventricle and the systemic circulation and thus we observe the significant attenuation of Stroke Work and ultimately these effects are indicative of further ventricular-vascular uncoupling. Furthermore, the enhancements in Effective Arterial Elastance  likely further attenuate not just transfer but the overall propagation of energy throughout the arterial system thereby limiting systemic perfusion and contributing to orthostatic and exercise intolerance.In this study we observed a diminished BCO induced pressor response likely due to the inability to increase cardiac output which was caused by significant reductions in stroke volume. Significant increases in heart rate were observed like as a compensatory mechanism to offset the afterload induced reductions to stroke volume. Additionally, we observed the increase in ventricular performance in healthy animals was significantly diminished in heart failure as observed by reductions in dP/dt MAX and MIN and a reduction in peak increase in end systolic pressure. Thus, the ability to regulate the ventricular component of the ventricular-vascular coupling relationship is likely nearly abolished in heart failure. In addition to these deficits, we observed that in response to BCO both indexes of Effective Arterial Elastance were significantly increased in control and, after the induction of heart failure, the increases in EWe used the classic technique of BCO to unload the carotid arterial baroreceptors in order to elicit baroreflex mediated autonomic responses. Previous studies utilizing an isolated carotid sinus technique in conscious dogs have shown that both the arterial pressure and heart rate responses to BCO are similar to those observed in response to reducing pressure in the isolated carotid sinus to sub-threshold levels . HoweverWe conclude that arterial baroreflex unloading at rest and during exercise acts to maintain ventricular-vascular coupling and thereby preserve blood pressure homeostasis by improving both ventricular and vascular aspects of the relationship. In heart failure significant ventricular-vascular uncoupling is apparent and drastically impairs any reflex increase in ventricular. Baroreceptor unloading in heart failure induces significant increases in Effective Arterial Elastance that in turn limit ventricular energy transfer as indexed by significant reductions in Stroke Work which likely inhibits propagation of ventricular energy throughout the arterial system. Thus, arterial baroreflex control not only is directly altered by the pathology of heart failure but also baroreflex-induced sympatho-activation actively worsens the ability of the reflex to improve perfusion pressure.


This review serves as a synopsis of multimodality imaging in cardiac amyloidosis (CA), which is a disease characterized by deposition of misfolded protein fragments in the heart. It emphasizes and summarizes the diagnostic possibilities and their prognostic values. In general, echocardiography is the first diagnostic tool in patients with an identified systemic disease or unclear left ventricular hypertrophy. Several echocardiographic parameters will raise suspicion and lead to further testing. Cardiac magnetic resonance and scintigraphy with bone avid radiotracers are crucial for diagnosis of CA and even enable a distinction between different subtypes. The subject is illuminated with established guidelines and innovative recent publications to further improve early diagnosis of cardiac amyloidosis in light of current treatment options. Cardiac amyloidosis (CA) is a disease characterized by deposition of misfolded protein fragments—called amyloid fibrils—in the heart. The two most frequent types of amyloidosis with cardiac involvement are light-chain amyloidosis (AL) and transthyretin amyloidosis (ATTR) . TTR amyAlthough AL and ATTR have similar effects on myocardial function and patients typically present with signs and symptoms of heart failure, they are different conditions with various therapeutic approaches. Thereby, early initiation of therapy is crucial for the prognosis . This isEndomyocardial biopsy is still considered the diagnostic ‘gold standard’, leading to the histological diagnosis of CA by Congo red staining. Despite its invasive nature, it is considered a fairly safe procedure if performed by an experienced examiner ,6. Due tThe purpose of this review is to summarize recent developments in available imaging modalities, highlight their advantages and disadvantages, provide a statement of diagnostic and prognostic value, and offer insight into recent work of various researchers. Transthoracic echocardiography (TTE) is widely available and can be performed in any setting, making it an excellent screening tool for initial evaluation. Increased thickening of the left ventricular wall, the interatrial septum, as well as the valves, and the presence of pericardial effusion are typical findings suggestive of CA . In addiMichele Boldrini and colleagues provide a multiparametric TTE approach for differentiation of patients with systemic AL from a hypertrophic phenotype. They found specific functional and structural TTE parameters characterizing different burdens of CA deposition to diagnose or exclude the diagnosis. The algorithm was developed to avoid unnecessary tests and limit the time to diagnosis, which is crucial for the patient’s prognosis .Strain evaluated by speckle tracking echocardiography (STE) presents an additional feature in the diagnosis of CA. A ‘speckle’ of myocardium identified by software is followed through a cardiac cycle to reveal information on its radial, longitudinal, and circumferential deformation. Therefore, a certain degree of image quality is necessary for conduction of STE. The characteristic STE pattern shows a reduction in global longitudinal strain (GLS) of the left ventricle in the basal and mid-ventricular segments with an apical sparing also called the ‘cherry-on-top’ sign and preserved left ventricular ejection fraction (LVEF).A small Spanish study of 40 patients with CA examined the performance of STE compared to cardiac biomarkers, such as brain natriuretic peptide (BNP) and cardiac troponin I, in the early diagnosis of CA. Strain values of both the right and the left ventricle seem to perform better than cardiac biomarkers . PagoureDespite the aforementioned possibilities, including the use of algorithms with highly sensitive and specific parameters, in most cases it is hardly possible to diagnose CA with echocardiography alone and further evaluation is needed.Transesophageal echocardiography can be performed for diagnosis in patients with suspected thrombus formation, but has an otherwise subordinate role compared to TTE. The formation of intracardiac thrombi, especially in the left atrium and the left atrial appendage, occurs frequently in patients with CA. Feng et al. examined 116 patients with CA post-mortem and found intracardiac thrombi in 33% of cases .Cardiovascular magnetic resonance (CMR) has several advantages compared to TTE. In most centers, it is used for further investigation of subjects with suspected CA and in patients with confirmed systemic amyloidosis. On one hand, it offers unmatched precision when it comes to measurements, including the assessment of the right ventricle; on the other hand, there is a unique opportunity of tissue characterization. The interobserver variability is presumably low, even in patients with a poor acoustic window. However, this does not apply to patients with cardiac devices or arrhythmias, which may impair the image quality due to artifacts.Standardized protocols for image acquisition are strongly recommended by the Society of Cardiovascular Magnetic Resonance (SCMR) . They noCompared to TTE, CMR provides more precise information about structural and functional abnormalities. Cine images are acquired by merging a number of stationary images taken at different cardiac cycles. They are reconstructed to map views familiar from TTE studies . The recommended measurements do not greatly differ from TTE assessment and include wall thickness, function and mass of the left ventricle, stroke volume index to body-surface-area, atrial size, and the presence or absence of pericardial effusion . TypicalIn addition to standard measurements, there is a trend towards process optimization using complex computer software for fully automated measurements, often based on machine learning algorithms. However, these have not yet reached the routine clinical process, so conventional analysis methods are still required. Our research group tried to find easy parameters derivate from CMR images independent of the aforementioned post-processing software. We evaluated the prognostic value of long-axis strain  and previously mentioned myocardial contraction fraction (MCF) in 74 patients with AL. All-cause mortality (primary endpoint) was significantly higher in patients with low MCF. Both impaired LAS and MCF were preserved as predictors for all-cause mortality and heart transplant .In analogy to speckle tracking in TTE, CMR uses feature tracking for strain analysis. ‘Feature’ refers to a certain myocardial pattern recognized and followed through a cardiac cycle by post-processing software to observe radial, circumferential, and longitudinal deformation of the myocardium. Like in STE, patients with CA being evaluated with CMR feature tracking typically show a pattern of relative apical sparing.In a study of 83 patients, Williams et al. compared CMR strain in patients with CA (45 patients), HCM, and Fabry disease . According to their findings, CA is associated with significantly lower longitudinal strain compared to both diseases. They also assessed the relative regional longitudinal strain ratio ) as an alternative parameter of the basal to apical strain gradient, with significant differences between CA and Fabry disease only .A small comparative study of 40 patients  conducted research on rotational mechanics of the left ventricle also using CMR feature tracking. The systolic movement around a longitudinal axis of the left ventricle is referred to as left ventricular twist (LVT). During systole, the LV base and the LV apex move in a clockwise and anticlockwise direction, respectively. The authors were able to demonstrate impaired LVT in patients with CA and increased LVT in patients with HCM .T1 mapping is an emerging tool used for tissue characterization and includes two sequences: native or pre-contrast T1 and post-contrast T1. Images are recommended to be acquired during diastole . VariatiPatients with systemic amyloidosis often have deposition of amyloid fibrils in the kidneys, leading to relevant renal dysfunction. This is an important limitation for the use of intravenous contrast agents. For the acquisition of native T1, none of them are necessary. It therefore takes an important diagnostic role when contrast agents are contraindicated. Native T1 displays not only extra- but also intra-cellular parts of the myocardium. Elevated T1 times are associated with the presence of CA. A very recent publication studied a large group of patients with suspected systemic amyloidosis. Though applied to selected individuals, high sensitivity and specificity were achieved  .T1 mapping is also believed to be a reliable tool for the monitoring of amyloid burden in AL during chemotherapy .Extracellular volume (ECV) is defined as extracellular matrix, water, and intracapillary plasma volume. ECV, but also intracellular volume, are dynamic and vary for different physiological and pathophysiological processes. Combining pre- and post-contrast T1 mapping enables the calculation of ECV. The patient’s hematocrit needs to be measured for that purpose. A normal ECV value for myocardium is around 25% . The depKorthals et al. compared receiver operating curves of native T1 and ECV as well as longitudinal strain and were able to illustrate superior diagnostic performance of native T1 and ECV over longitudinal strain . They eaGadolinium-based contrast agents (GBCA) are administered intravenously following predefined protocols. In the literature, cases of nephrogenic systemic fibrosis, a rare kidney disease with poor prognosis, after the use of GBCA are described. It remains a controversial subject . Recent Phase-sensitive inversion recovery (PSIR) is used to overcome problems with ‘myocardial nulling’. Difficulties in ‘myocardial nulling’ are typical for CA and describe the challenge of finding an inversion time to differentiate the myocardium from the blood pool when acquiring images with GBCA .Myocardial uptake of gadolinium is referred to as late gadolinium enhancement (LGE). The accumulation of amyloid fibrils leads to the expansion of extracellular space, where gadolinium uptake experiences regional differences depending on the extent of expansion. Patterns range from typically described subendocardial to diffuse, transmural, or patchy dispersion. Though discrimination between different types of CA is not reliably feasible, a study including almost one hundred patients with cardiac involvement of amyloidosis demonstrated that LGE is more extensive in patients with ATTR and there is a higher proportion of patients showing transmural patterns of LGE . TransmuT2 mapping is another quantitative tool used for tissue characterization. T2 times are tissue-specific and enable differentiation between normal and abnormal myocardial tissue. Water has quite a long T2 time. Therefore, the tissue has a higher content of water, hence myocardial edema can be depicted by this technique. Reference values for T2 times are different for 1.5 and 3 T MRT scanners . KotechaA meta-analysis by Brownrigg et al. analyzed the performance of CMR in differentiating AL and ATTR  and compared CMR to scintigraphy  . In summNuclear imaging is a generic term for several imaging techniques. They all make use of small amounts of radioactive tracers administered to gain information about organs and tissues and represent an additional pillar in the diagnosis of CA. Nuclear imaging is not about functional, but more about structural assessment. While scintigraphy is two-dimensional or planar, positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are three-dimensional.Scintigraphy is recommended in patients with suspected CA due to findings from TTE and CMR. In addition, patients with confirmed ATTR neuropathy or a positive test for a TTR gene mutation are also advised to undergo scintigraphy. Otherwise, it should also be considered in case of unexplained left ventricular wall thickening, bilateral carpal tunnel syndrome, and for individuals with a family history of amyloidosis .Today, three bone avid radiotracers are used to perform scintigraphy in patients with suspected CA . All of In the late twentieth century, knowledge about scintigraphy for the diagnosis of CA was not consolidated. A study from 1987 by Gertz et al. serves as an example by showing that only a loose association between scintigraphy and CA was established . FurtherA large study published in 2016 highlighted the performance of scintigraphy for the diagnosis of cardiac ATTR. The combined finding of Grade 2 or 3 radiotracer uptake in the absence of monoclonal protein in serum and urine is associated with a specificity and a positive predictive value for ATTR CA of 100%. Radiotracer uptake alone had a sensitivity of >99% and a specificity of 86% for ATTR CA. False positive cases almost exclusively occurred in patients with AL CA . EspeciaIn addition, radiotracer uptake correlates positively with all-cause mortality and negatively with survival free of cardiac adverse events . Another11C-Pittsburgh Compound B, 18F-Florbetapir, and 18F-Florbetaben are amyloid-binding radiotracers. They were not designed for cardiac imaging but, i.e., for imaging of beta-amyloid deposits in the brain in Alzheimer’s disease. PET is a functional nuclear imaging technique using computed tomography (CT) or magnetic resonance tomography (MRT), which is therefore not only eligible for CA but also systemic amyloidosis. Amyloid-binding radiotracers enable a quantification of the global amyloid burden but also of a regional burden, such as the myocardium. The parameters measured are the self-explanatory target-to-background ratio, myocardial standard uptake value , and myocardial retention index (derived from SUV in different phases after radiotracer injection). The direct binding of the tracers to the agent causing the disease allows early detection of the disease, even before structural changes appear. Early detection is crucial for effective treatment. Distinction between the different types of CA is not feasible with this technique. Due to possible quantification of deposits, PET has the potential for serial imaging in order to monitor response to treatment .Singh and Dorbala provide an overview of several studies conducted on PET in CA. The studies are limited by small sample sizes and a lack of standardized protocols for image acquisition. This can be illustrated with one specific publication commented on in the above work, which studied a new radiotracer (amyloid-binding 18F-Flutemetamol) in only 17 patients undergoing PET (with CT or MRT). Images were acquired more than one hour after injection of the radiotracer, which is rather late compared to other amyloid-binding radiotracers. Only a small percentage of patients with CA showed relevant radiotracer uptake ,42,43.However, further research with larger sample sizes and standardized protocols is needed before PET is applied in clinical routine.If the suspicion for CA is raised by clinical, laboratory, electrocardiographic, and very often echocardiographic findings, a multitude of imaging techniques can be applied to confirm the diagnosis and to differentiate between different types of amyloidosis non-invasively, such as CMR, scintigraphy, and PET.CMR is able to reveal the structure and function of the chambers and to quantify amyloid deposits. The administration of GBCA is limited due to the high incidence of impaired renal function in patients with amyloidosis. Scintigraphy with bone avid radiotracers in combination with laboratory testing offers accurate diagnosis of cardiac involvement in ATTR amyloidosis. PET using amyloid-binding radiotracers has a subordinate role but enables early detection and quantification. Advantages and disadvantages of all imaging modalities have been listed in Current guidelines recommend CMR especially for the differentiation of CA and other cardiac pathologies. Scintigraphy should be performed in patients with suspected CA in the absence of a monoclonal light chain. The use of PET is only mentioned in the context of disease progression and the response to treatment ,38.CMR and scintigraphy allow an estimation of prognosis. Radiotracer uptake in scintigraphy correlates with all-cause mortality . LGE, na


Recent studies have shown that the neutrophil-to-lymphocyte ratio (NLR) has gradually been identified as a more reliable marker of inflammation, with predictive value for the development of many diseases. However, its association with left ventricular (LV) diastolic dysfunction in overt hyperthyroid patients is unclear. Here, we aimed to explore the relationship between NLR and LV diastolic dysfunction in overt hyperthyroid patients.For this study, we retrospected the consecutive medical files of 350 overt hyperthyroid patients. Their medical data and laboratory findings were recorded. According to the presence or absence of LV diastolic dysfunction, the patients with overt hyperthyroidism were divided into two groups. One group with LV diastolic dysfunction included 104 patients and another group with non-LV diastolic dysfunction included 246 patients. The NLR values between the two groups were compared, and the relationship between NLR levels and the prevalence of LV diastolic dysfunction was also explored.The NLR value in LV diastolic dysfunction group in the overt hyperthyroid subjects was significantly higher than that in non-LV diastolic dysfunction group . The prevalence of LV diastolic dysfunction in Low- (NLR<0.879), Medium- (0.879< NLR<1.287), and High- (NLR >1.287) NLR level groups were 20.9%, 32.5% and 35.7% respectively. Moreover, increased NLR is associated with increased prevalence of LV diastolic dysfunction, and after adjustment for potential associated factors, NLR remained significantly associated with LV diastolic dysfunction. .Our findings demonstrated that the NLR was associated with LV diastolic dysfunction in the overt hyperthyroid patients, and the prevalence of LV diastolic dysfunction may be positively correlated with NLR levels. Hyperthyroidism, one of the most common endocrine disorders, is reported that the prevalence ranges from 0.2%-1.3% in iodine-sufficient regions of the world . In patiMultiple mechanisms might be involved in the pathogenesis of cardiovascular disease in the overt or clinical hyperthyroid patients, and growing studies have revealed that chronic low-grade inflammation induced by metabolic disorders might have a critical role . And theThis study complied with the Declaration of Helsinki and was approved by the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology. We reviewed consecutive medical records of inpatients in the Department of Endocrinology, Wuhan Union Hospital, China from May 2018 to May 2019. Our study ultimately included 350 patients who received 131I treatment for overt hyperthyroidism. Subjects who were newly discovered and diagnosed with overt hyperthyroidism and/or who had been off antithyroid drugs for 4 or more weeks were finally enrolled in the analysis. Our research adopted the definitions in the American Thyroid Association(ATA) Guidelines , overt h2), normal (18.5–24.0 kg/m2), overweight (>24.0 kg/m2) , systolic blood pressure (SBP), diastolic blood pressure (DBP), neutropenia or agranulocytosis and impaired liver function. BMI was calculated by dividing weight (kg) by the square of height (m). BMI was divided into thin (<18.5 kg/m0 kg/m2)  in line We reviewed the consecutive medical files of the patient’s echocardiographic data. All echocardiographic examinations were performed during hospitalization on enrolled patients adopting echocardiographic systems  and 3-8 MHz transducers. Signs of diastolic dysfunction based on the E/A ratio value of the mitral and/or the e/a ratio value of the septal basal regions were performed by two experienced ultrasound doctors. The cutoff value below 1 indicates impaired myocardial relaxation , 16. TheAll statistical analyses and graphs were performed with IBM SPSS 24.0 and GraphPad Prism 7.0. Assessing whether a continuous variable is normally or non-normally distributed by the Kolmogorov-Smirnov test. Data that are normally distributed are expressed as mean ± standard deviation (SD), while data that are skewed are expressed as median (25th-75th percentile). Data are categorical and expressed as numbers or percentages as shown. For analysis of the independent variables, the differences between groups were compared using Student’s t-test, Mann-Whitney U test, Kruskal-Wallis test, or chi-square test, as appropriate. Spearman’s correlation analysis was undertaken to explore the associations between thyroid hormone and other clinical parameters. The relationship between NLR and LV diastolic dysfunction was conducted by univariate and multivariate logistic regression analysis. Statistical significance is set at P-values < 0.05.By May 2019,603 patients with abnormal thyroid function were admitted. After excluding 142 cases diagnosed with other thyroid diseases,30 cases diagnosed with subclinical hyperthyroidism, and 81 cases without hematologic or echocardiography results, a total of 350 individuals with overt hyperthyroidism were included in the analysis Figure 1In the comparison of leukocyte-derived inflammatory parameters, subjects with LV diastolic dysfunction had significantly lower PLT, monocyte, and lymphocyte counts (both P <0.05). Compared with those without LV diastolic dysfunction, subjects with LV diastolic dysfunction had higher NLR (P = 0.016) Table 2.Univariate logistic regression analyses revealed that age, duration of hyperthyroidism, BMI, SBP, Scr, PLT count, lymphocyte count, and NLR were all positively correlated with LV diastolic dysfunction in the overt hyperthyroidism subjects. A multiple logistic regression analysis revealed age, duration of hyperthyroidism, BMI, neutrophil count, and NLR may be independent risk factors for the development of LV diastolic dysfunction Table 3.According to admission NLR value,350 subjects were divided into tertiles. NLR<0.879 (n = 115), 0.879< NLR<1.287 (n =120), NLR >1.287 (n = 115) were defined as the low, medium, and high NLR level groups, respectively. Among the patients with overt hyperthyroidism, the prevalence of LV diastolic dysfunction in the low, medium and high level groups were 20.9%, 32.5% and 35.7%, respectively Figure 2The demographic features and laboratory test results of the overt hyperthyroid patients in the three NLR level groups are presented Table 4.In this retrospective study, we explored the association between NLR and LV diastolic dysfunction in overt hyperthyroid patients. Our study revealed that NLR values are independently associated with LV diastolic dysfunction in subjects with overt hyperthyroid in a dosage-related manner. The results suggested that NLR may be used as an auxiliary indicator in the early diagnosis of LV diastolic dysfunction in the overt hyperthyroid subjects.131I treatment. Our study showed the value of E/A is low in the patients with LV-diastolic dysfunction, compared with the patients with no LV diastolic dysfunction. The value of E/A is decreased by the LV-diastolic dysfunction. It reminds us that impaired myocardial relaxation  patients whose NLR increased had worse prognosis than non-increased patients . NLR is Hyperthyroidism enhances the activity of key cells of the innate immune system  and the activity and proliferation of important cells of the adaptive immune system (namely B- and T- lymphocytes) . Hence, Our study found that higher NLR values were associated with greater odds of LV diastolic dysfunction in subjects with overt hyperthyroidism, which may suggest that innate immunity-induced inflammation may make a critical impact on the development of LV diastolic dysfunction in overt hyperthyroid patients. Previous studies showed TH plays an important role in the innate immune system . A recenThere are also some limitations as follows in this study. First of all, the sample size is too small to illustrate the relationship between NLR and LV diastolic dysfunction in subjects with overt hyperthyroidism, so larger studies are needed for further evaluation. Secondly, our research is a cross-sectional study, so in the future, a prospective study is required to explore the NLR levels after getting therapy or with further deterioration of LV diastolic dysfunction. Tertiary, due to the limitations of ultrasound technology and measurements at the time, LV diastolic dysfunction by modalities was still insufficient to assess in this study, we believe that this theoretical bias has a limited impact on the results. And we are unable to obtain sufficient and sufficient data in the diagnosis and classification of left ventricular diastolic dysfunction. In addition, other common inflammatory factors and immune mediators were not measured in our study.In summary, our findings demonstrated that NLR is strongly associated with LV diastolic dysfunction in subjects with overt hyperthyroidism and that the prevalence of LV diastolic dysfunction is positively correlated with NLR levels. Our research demonstrated that NLR may be used as an auxiliary predictor of LV diastolic dysfunction in patients with overt hyperthyroidism and may be applied in clinical practices to assist physicians in monitoring the development and progression of LV diastolic dysfunction.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.This study complied with the Declaration of Helsinki and was approved by the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology. The patients/participants provided their written informed consent to participate in this study.JZ, LW, and YL conceived and supervised the study. HL and HZ collected the epidemiological and clinical data. HZ, HL, JZ, and YB summarized the data. HZ did data analysis and draft the manuscript. JZ, LW, and YL revised the final manuscript. All authors contributed to the article and approved the submitted version.Funding to support this survey was provided by the Natural Science Foundation of Hubei province (2013CFB091) which was funded by the Science and Technology Department of Hubei.The 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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. 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