Transcatheter tricuspid intervention is a rapidly evolving field with multiple classes of therapeutic devices currently in development. Procedural success in tricuspid intervention is predicated on appropriate device selection for patient specific anatomy and satisfactory imaging for intra-procedural guidance. This review will outline protocols and methodology for multi-modality imaging assessment of the tricuspid valve and associated structures, with emphasis on anatomic and functional characteristics that determine suitability for each class of tricuspid intervention. Intra-procedural imaging requirements for each class of device, with design and procedural imaging guidance of specific devices, will also be addressed. Tricuspid regurgitation (TR) is associated with increased mortality even after adjustment for left heart disease , 2. SurgThe TV is the largest cardiac valve with normal function dependent on the leaflets, annulus, papillary muscles, and chordae , 12. TheIdentification of the anterior papillary muscle can be performed by size (largest), location on the anterolateral right ventricle (RV) wall, and incorporation into the moderator band. RV dilatation, particularly of the mid-ventricular free wall, may thus cause the papillary muscle to be more apically positioned, stretching the chordal attachments to the anterior and posterior leaflets, and causing tethering of the leaflets in systole. A variable number of posterior papillary muscles send chordal attachments to the posterior leaflet(s) and posterior segment of the septal leaflet. The septal and anterior leaflets also receive chordal attachments from septal papillary muscle(s) or from direct septal chordal attachments. Changes in position of the interventricular septum may affect the systolic mobility of the septal leaflet.The normal TV annulus is a saddle-shape, ovoid structure , 17 whicTR classification can be established from morphological and functional assessment of the tricuspid leaflets, right atrium (RA), and RV, and is an important characterization that guides TTVI device selection. TR may be classified as primary, secondary or cardiac implantable electronic device (CIED)-related  22, 23), 2322, 2Secondary TR (STR) accounts for >85% of cases of severe TR and may be atrial or ventricular in origin. Atrial secondary TR is characterized by right atrial and tricuspid annular dilation resulting in a mismatch between tricuspid annulus and tricuspid leaflet area. Atrial STR is typically observed in patients with chronic atrial fibrillation (AF). RV basal dilation and “conical” RV morphology is observed in these patients; however, leaflet tethering is rare until late in the disease , 27. ForVentricular STR is characterized by “spherical” mid-apical RV dilation with apical papillary muscle displacement and leaflet malcoaptation from tethering. Ventricular STR is typically observed in the setting of pulmonary hypertension , 27. RigA comprehensive evaluation of the TV should be performed by transthoracic (TTE) as well as transesophageal echocardiography (TEE). Adjunctive imaging tools include echo-fluoro fusion and 3D intracardiac echocardiography (ICE). TEE should be performed in all patients under consideration for transcatheter TV intervention (TTVI) to establish the severity and classification of TR, assess leaflet morphology and characteristics, TR jet size and location, and annular size. These anatomic parameters may permit patient-specific optimal device choice. Intra-procedural TEE with live three-dimensional (3D) multi-planar reconstruction (MPR) is critical for pre-procedural imaging  as well TEE assessment of the TV is complicated by the position and characteristics of the valve. As the largest and most anterior of the cardiac valves, the posterior position of the TEE probe requires far field imaging with acoustic shadowing from the interatrial septum or intervening left heart structures, as well as tangential imaging of the annular plane which relies on more limited lateral resolution. In addition, large 3D volumes must be obtained to encompass the entire valve and adjacent structures. To overcome these limitations, comprehensive TEE examination of the TV requires dedicated imaging from multiple esophageal and gastric levels. A detailed imaging protocol for tricuspid assessment is outlined in the American Society of Echocardiography guidelines, which, in brief, recommend multiplanar imaging from; the mid-esophageal window to evaluate the TV and RV in relation to surrounding anatomic structures, the distal esophageal window to eliminate intervening left-sided cardiac structures from view and optimize visualization of the tricuspid leaflets, the transgastric level for 2D/3D en face imaging of the TV and chordae attachments, and the deep transgastric window for both leaflet/subvalvular imaging and optimization of color and spectral evaluation of TR jets  33)..33).3D rendering of the tricuspid valve allows for rapid morphologic assessment and anatomic orientation. The use of advanced 3D manipulation with MPR of the 3D volume, is crucial for pre-procedural quantitative assessment of tricuspid leaflets and annular sizing , as well as intra-procedural guidance of TTVI performed real-time.en face view of the TV. There are 2 common orientations of this en face view; the surgical perspective which rotates the image to place the aortic valve in the near field at ∼11 o'clock, or a non-rotated view where the aortic valve is at 5 o’clock (similar to a transgastric short-axis view).Acquisition of 3D volumes should be performed from any imaging level with high quality 2D imaging. The acquired volume should include surrounding anatomical structures, ideally the aortic valve, in order to assist in 3D orientation . Once geFor quantitation assessment of the tricuspid valve, a 3D volume can be manipulated off-line using MPR. Measurement of annular area, perimeter and diameters, as well as quantitation of leaflet lengths and coaptation gaps are required for determining anatomic feasibility of device placement. For procedural guidance, real-time multiplanar imaging using MPR allows continuous imaging of four different views: two orthogonal 2-D long-axis views with the tricuspid annulus perpendicular to the ultrasound beam, a 2D short-axis view at any level of the tricuspid valve apparatus, and a 3D rendered image. The most useful 2D long-axis views are typically the inflow-outflow view imaging the anterior leaflet to the right, and posterior leaflet to the left of the sector, and the orthogonal 4-chamber view with “lateral” leaflet to the right, and septal to the left of the sector. The “lateral” leaflet can be either the anterior or the posterior leaflet depending on the where the orthogonal plane is placed on the inflow-outflow view. The short-axis view can be positioned at any level, from the narrow apex to the broad base of the volume, depending on the requirements of device positioning and anchoring; imaging the annular level is most useful for annuloplasty devices and orthotopic valve replacements whereas at the leaflet level may be optimal for TEER devices. The 3D rendered image can be defined by the user as any of the three 2-D images in the MPR screen but most often the short-axis 3D rendering is preferred for TEER devices to orient the device arms and for orthotopic valve replacements for positioning in the annulus. Importantly, all planes can be manipulated throughout the procedure to inform the proceduralist of device positioning relative to the tricuspid valve and surrounding anatomy.Quantitation of TR severity is necessary to establish pre-procedural baseline and inform prognosis. Contemporary classification of TR severity involves a five-grade scale, extending the traditional “mild”, “moderate” and “severe” with “massive” and “torrential” grades, with severity established through a combination of quantitative parameters  34). Me. Me34). Evaluation of TV morphology and leaflet assessment is crucial to inform transcatheter device selection and should be systemically evaluated in all pre-procedural TEE examinations. A useful technique for leaflet assessment is biplane imaging from the mid or distal esophageal inflow-outflow view  of the TV, which is typically acquired at 50–80 degrees of mechanical rotation. Using simultaneous biplane imaging, sweeping the orthogonal imaging plane from posterior (left side of sector) to anterior  visualizes the coaptation of the posterior-septal, then anterior-septal commissures, respectively . In thisTransgastric imaging facilitates evaluation of TV morphology and further localization of the origin of TR. From the mid-gastric window, right flexion and anteflexion of the TEE probe produces a right ventricular inflow view with the tricuspid annulus parallel to the insonation beam. Biplane imaging through the tricuspid annulus then produces an en face view of the TV . The en RV function is an important determinant of patient outcome following TTVI. Assessment of RV function may also serve as a useful clinical tool to guide timing and risk stratification of TTVI. Because longitudinal shortening is a dominant mechanism of RV ejection, tricuspid annular plane systolic excursion (TAPSE) as well as tissue Doppler s' and RV free wall strain are important echocardiographic measures to assess RV function . ReductiPropensity matched analysis from the TriValve registry suggests the degree of RV dysfunction in patients undergoing TTVI may be an important parameter influencing post-procedural outcomes. In the TriValve registry, TTVI in patients with mid-range reduced TAPSE of 13–17 mm was associated with survival advantage compared to conservative therapy at one year. In contrast, TTVI in patients with TAPSE < 13 mm conferred no survival advantage . The absTAPSE has numerous limitations for RV assessment, being dependent on Doppler alignment for accuracy and non-reflective of radial RV contraction. Alternate markers of RV function may better predict outcomes and guide selection for TTVI. In a prospective cohort of 75 patients undergoing tricuspid TEER in which all patients had 3D RV ejection fraction at baseline, 3D RV ejection fraction of <44.6% predicted mortality at one year, whereas TAPSE did not . RV freep < 0.001) after correcting for potential confounders. Recent analysis of a TTVI registry demonstrates that a low RV-PA ratio of <0.406 at baseline is a powerful predictor of post-procedure shock and of all-cause mortality at one year following TTVI, and may be a robust tool to guide patient selection and procedural timing  coupling reflects the efficiency with which RV stroke work is transferred into the PA and can be calculated echocardiographically as the ratio of TAPSE: pulmonary artery systolic pressure (PASP). In compensated states, increase in RV afterload from rising PASP is associated with a proportionate increase in RV contractile function, reflected by TAPSE. As the RV decompensates, however, there is uncoupling of afterload and RV contraction, and the RV-PA ratio declines. In a large study of medically managed patients with TR, a TAPSE/PASP value <0.31 mm/mm Hg was used to define RV−PA uncoupling and to dichotomize the population . RV-PA ul timing .Annular area by TEE can be estimated from 2D imaging by incorporating the anterior-posterior and septal-lateral annular diameters into the formula for an ellipse, or measured from 3D volumes . Two metCT facilitates anatomical assessment of the TV complex, RV, and associated vascular structures. CT is requisite in all TTVI planning, excluding TEER. CT may also play an adjunctive role in evaluating TR severity and RV function in cases of suboptimal echocardiographic assessment.Multiphasic electrocardiogram (ECG)-gated acquisition should cover the entirety of the cardiac cycle. This can be performed using ECG-triggered prospective acquisition or retrospective helical scanning; the latter preferred if cine images are required . More adImage acquisition may be challenging due to the presence of AF or intracardiac devices, both of which are frequently concurrent with TR. In the case of AF or other tachyarrhythmia, the use of retrospective ECG-gated protocols is preferentially used, albeit at a higher radiation dose .Clear visualisation of the right heart and TV requires a dedicated CT protocol to ensure adequate contrast opacification around the TV annulus and minimise artefacts. Intravenous injection of a standard non-ionic contrast agent with an iodine concentration of 270 to 370 mg/ml is used. A triphasic protocol   yields oDirect quantification of TR severity using cardiac CT is not widely established. CT features suggestive of TR include RA and RV dilation, reflux of contrast media into the inferior vena cava (IVC), and dilated hepatic veins. Opacification of the hepatic veins and IVC on first-pass arterial phase CT imaging is suggestive of TR with high specificity and sensitivity . Other aThe AROA is a novel marker of TR severity which measures the defect area in tricuspid leaflet coaptation. AROA is measured dring mid systole  via planimetry of the minimum area bordered by the tricuspid leaflet tips in the short-axis view defined by double-oblique multiplanar reconstruction . Recent Tricuspid leaflet tethering area and height are assessed on the long-axis two- or four-chamber view images by measuring the distance between the annular plane and leaflet coaptation point, and by tracing the leaflets from the annular plane, respectively . TricuspThe tricuspid annulus area is measured from reconstructed short-axis imaging obtained at mid diastole  with manual selection of the plane at the level of the TV annulus on the four-chamber and two-chamber views. The normal maximum annulus diameter is 3.0–3.5 cm on the short-axis image. Functional TR is characterised by annular dilation >4 cm .RV morphology assessment is required for planning orthotopic TV replacement. Necessary assessment includes measurement of RV length, assessed in the four-chamber view at end systole as the distance between the tricuspid annulus and perpendicular RV apex, and evaluation of anatomic structures including papillary muscles and the moderator band, within this path . RV ejecLocalization of the course of the right coronary artery (RCA) is crucial in assessment of TTVI to evaluate risk of coronary impingement during implantation of the annular anchoring systems. MPR of the two-, four-chamber, and short-axis views of the TV during mid diastole are evaluated to measure the distance between the RCA and the annulus. Unfavorable course of the RCA is described as <2 mm distance to the annulus and occurs most commonly in association with the posterior TV leaflet given its position along the diaphragm .Evaluation for TTVI requires assessment of central and peripheral venous anatomy for device delivery. Device specific evaluation may include assessment of femoral or jugular vein diameters, cavo-atrial angulation, or detailed evaluation of caval anatomy. Orthotopic tricuspid valve replacement typically requires large bore peripheral venous access. Orthotopic tricuspid valve replacement and TEER are complicated by acute cavo-atrial angulation , 59. HetCMR is not routinely indicated for pre procedural evaluation of TTVI, however, may be used in an adjunctive role to guide patient selection through assessment of right ventricular function and TR severity. Right ventricular image acquisition is performed with cine steady-state free-precession sequencing. Volumetric analysis is performed from stacked short-axis cine images from the base to the apex of the right ventricle, obtained separately using ECG-gated acquisitions. The endocardial margin of each slice is traced at both end-diastole and end-systole. Post-processing software is used to calculate the RV volume, mass, and ejection fraction . CMR is Fluoroscopic projections of the right ventricular long axis perpendicular to tricuspid annulus and of the en face tricuspid annulus should be established during TTVI for assessment of device positioning and axiality with the tricuspid annulus. These projections may be derived from the pre-procedural CT and are typically the right anterior oblique cranial (RAO/CRA) and left anterior oblique caudal (LAU/CAU) views, respectively , 63. RoaTwo-dimensional ICE has been used as an adjunct to TEE imaging for TTVI , 67. ThrA number of recent single-site surgical reports suggest with careful patient selection, advanced surgical techniques and periprocedural management, isolated TV surgery can be performed with lower morbidity and mortality , 69. HowLeaflet approximation is most commonly performed via TEER. Other novel devices for enhanced leaflet coaptation currently under investigation are considered under “miscellaneous therapies” later in this review. Anatomic determinants of suitability for leaflet approximation devices are outlined in The TriClip system consists of a steerable guide catheter and clip delivery system including an implantable clip. The clip is composed of two clip arms and grippers with vertically arrayed retention elements. Four clip sizes are available: the NT and NTW, featuring 9 m clip arms with 4 and 6 mm widths, respectively, and the XT and XTW, featuring 12 mm clip arms and 4 and 6 mm clip widths, respectively. The grippers can be actuated simultaneously or independently. Results from the TRILUMINATE Pivotal Trial which randomized patients with severe, symptomatic TR to TriClip or medical therapy, confirmed the safety of the device and showed a significantly improved patient quality of life at one year, but failed to show an improvement in mortality or heart failure hospitalizations compared to medical therapy . This maThe PASCAL repair system consists of a guide sheath, steerable catheter, and implant catheter. The device implant is composed of a central spacer designed to reduce leaflet stress with adjacent paddles and clasps. The clasps have a horizontal row of four retention elements at their tip to enhance leaflet capture. Two sizes are available: the PASCAL Ace, with 6 mm wide and 15 mm long paddles, and the PASCAL, with 10 mm wide and 16 mm long paddles. The clasps can be actuated simultaneously or independently. Both devices can be elongated when positioning and manoeuvring to reduce risk of chordal entrapment. The randomized controlled CLASP II TR trial  is currently enrolling with a 2-year composite endpoint.TEER relies on feasible leaflet anatomy and TEE image quality for procedural success. Cardiac CT and CMR are typically not required in pre-procedural evaluation.Pre-procedural TEE should be performed with the patient in minimal lateral positioning, or, if tolerated, supine, to replicate the conditions available for intra-procedural imaging. For procedural success in TEER, adequate tricuspid leaflet visualisation must be available from at least one esophageal level and from the transgastric level, although guidance of TEER may be feasible with sub-optimal esophageal windows if 3D ICE is available. TEE assessment should be performed as per protocol outlined above. Anatomic characteristics influencing favourability for TEER are outlined in Procedural assessment should begin with full comprehensive TEE examination including formal quantitation of TR severity while under anaesthesia to establish a baseline for post-procedural comparison.Procedural guidance begins as the device delivery system enters the RA from the IVC. Imaging at this stage is necessary to assess device trajectory and ensure the device does not damage the intra-atrial septum, or interact significantly with the Eustachian valve, Chiari network, pacing hardware, or other RA structures which may restrict movement of the device. Imaging is obtained by acquiring a bicaval view from the mid-esophageal window before lowering the mechanical rotation and retro-flexing the probe until visualization of the IVC and RA junction is optimized. Once the device is located, live 3D or biplane imaging should be employed to track the device relative to the tricuspid annuls as it is manoeuvred superiorly to the mid-atrial level. Once the device has reached mid RA level, flexion of the delivery catheter will lower the device towards the tricuspid annulus. This may be tracked by anti-clockwise rotation of the TEE probe, bringing the TV into view. The imager should then pause, optimize imaging windows, and evaluate the optimum location for TEER.The optimal location for TEER may be denoted by specific anatomic characteristics, such as the location of a flail segment, or the location at which colour Doppler suggests the TR is most severe. In the absence of a specific anatomic defect, or in cases where the TR is diffuse, anterior-septal TEER may be the most effective initial step in reducing TR . TEER reen face image should be positioned at the intended site of repair and orientated at the intended angle of device deployment, which, to preserve leaflet geometry, should typically be perpendicular to the line of coaptation. Leaflet characteristics  at the intended site of TEER will then be appreciable in the corresponding imaging plane. If characteristics at the initial site of assessment are unfavorable, dragging the perpendicular plane across the breadth of coaptation facilitates “scanning” of the tricuspid leaflets to identify a feasible site for repair.Leaflet assessment at the site of intended site of TEER, and guidance of the device to this location, is most effectively performed with 3D MPR. To assess, the MPR cross hair in the Once the site for repair has been established, the device should be maneuvered to this location using the MPR crosshairs as a guide. The open device arms orientation should be aligned with the established MPR configuration at the optimum site for repair. Short-axis transgastric imaging can also be used to evaluate orientation. Independent grasping controls should be confirmed prior to advancing the device into the RV.The device should then be advanced below the valve and orientation re-assessed. Two different methods can be used; (1) 3D volumetric imaging from esophageal levels of imaging, which typically requires reducing the 3D gain resulting in dropout of the thin TV leaflets and clear imaging of the device in the RV, and (2) 2D short-axis transgastric imaging of the leaflet tips to evaluate device orientation, with the caveat that off-axis imaging of the valve may lead to inaccurate position assessment. Once orientation is confirmed, the device is retracted toward the leaflet, avoiding chordal entanglement and visualizing leaflets laying flat  on the device arms/paddles.en face views, while imaging trajectory and leaflet engagement in orthogonal 2D long-axis views. In some cases, however, 3D MPR resolution is inadequate to assess leaflet engagement. In such cases, 2D single plane , or biplane imaging using the commissural view as the primary image and the biplane marker directly through the device to display leaflet engagement in the orthogonal plane, may be used. With either technique, the imager should look to demonstrate leaflet tissue laying on the device base arms/paddles before leaflet capture is performed. Unlike TEER for the mitral valve, the “bouncing” of the grippers/clasps due to systolic closure of the captured native leaflets may not be seen on the low pressure right side. If repeated attempts at leaflet capture are unsuccessful, device rotation should be suspected, and orientation reassessed.Leaflet capture may be performed under 3D MPR or 2D single or biplane imaging. 3D MPR has some advantages to 2D imaging as it facilitates continuous surveillance of device orientation on short-axis or 3D Post-deployment assessment includes evaluation of the severity of residual TR, tricuspid gradients and valve area, RV function, and hemodynamic benefits. TR quantitation following TEER is most accurately assessed by 3D planimetry of the vena contracta area, as the regurgitant orifice area by PISA may be distorted by the TEER device typically overestimating severity, and the diastolic stroke volume cannot be accurately measured for quantitative assessment given the distortion of the inflow by the device. Tricuspid gradients and valve area are rarely significantly elevated following deployment of a single device. RV function is typically unchanged unless there is a dramatic reduction in TR severity with an associated significant increase in effective RV afterload. Reduction in hepatic vein reversal, and increased RV and LV stroke volume, are indicative of successful repair.A number of orthotopic tricuspid replacement devices are currently in development. The devices rely on either radial force, tricuspid leaflet engagement, or septal insertion for implantation and stability. Anatomic determinants of suitability for orthotopic TV replacement are displayed in The EVOQUE system  consists of an implantable bioprosthetic valve, steerable delivery catheter, and dilator kit. The valve element is composed of a trileaflet bovine pericardial valve mounted on a self-expanding nitinol frame with a fabric skirt. There are nine anchors on the ventricular portion of the valve frame for native leaflet capture and device anchoring. The system is delivered via 28Fr femoral venous access and is available in three sizes: 44, 48, and 52 mm. Of the devices currently in trial or development, the EVOQUE system currently has the greatest body of clinical evidence, with results from the single arm TRISCEND study of 176 patients demonstrating excellent device efficacy and safety out to one year, including; survival of 90.1%, freedom from heart failure hospitalization at 88.4%, and significant and sustained TR reduction, with 97.6% of patients with mild or trace TR –77. The Procedural imaging guidance is performed with fluoroscopy and TEE. The device is advanced via the delivery steerable catheter across the tricuspid annulus into the right ventricle. Device location, depth, and axiality are optimized with imaging. The device anchors are exposed through retraction of the delivery capsule and positioned below the tricuspid leaflets and above the papillary muscle heads. Further device expansion then positions the anchors below the annulus for native leaflet capture. Leaflet capture by all nine anchors is assessed by 3D MPR by rotation of the MPR lines on the short-axis image with the crosshair placed in the centre of the device at the level of the anchor tips, sequentially demonstrating leaflet engagement and annular position of each anchoring element on the long-axis orthogonal views. After satisfactory leaflet capture is confirmed, the device is fully expanded and released from the delivery system. Valve hemodynamics, valvular and paravalvular regurgitation are assessed as per standard protocols.The LuX-Valve  is a bioprosthetic valve and stent prosthesis composed of a trileaflet bovine pericardial valve, a self-expanding nitinol valve stent with an atrial disc, an interventricular septal anchoring element, and two clips for anterior leaflet attachment. The implant relies on the septal anchoring element and leaflet clips, rather than radial force, for attachment and stability. Early iterations of this device used minimally invasive right thoracotomy for transatrial access , 79. RecIntra-procedural imaging is performed combining fluoroscopy and TEE to assesses device location, orientation, and trajectory. After access and introduction of the delivery system into the RV, the system is centred in the tricuspid annulus perpendicular to the annulus. The outer sheath is then withdrawn, releasing the valve stent, anchoring elements, and leaflet clips. The leaflet clips are then expanded and the system withdrawn towards the tricuspid annulus, facilitating leaflet clip capture of the anterior leaflet. The leaflet clips may be visualised to “swing” with the motion of the anterior leaflet on fluoroscopy or TEE when capture is successfully performed. After leaflet capture is confirmed, the atrial disc is released. Optimization of the orientation axiality of the implant within the tricuspid annulus is then performed. Once positioning is satisfactory, a nitinol anchor is fired from the anchoring element into the ventricular septum, securing and finalizing deployment of the valve. Following deployment, valve hemodynamics, valvular, and paravalvular leak are assessed as per standard protocols.The Cardiovalve  is a trileaflet bovine pericardial valve mounted on a dual self-expanding nitinol frame composed of welded ventricular and atrial elements. The ventricular frame has 24 grasping legs for tricuspid leaflet engagement and the atrial frame has a dacron fabric covered flange for anchoring and sealing. The valve is delivered through 28Fr transfemoral access. Three sizes of 45, 50 and 55 mm are available , 81.The device is advanced via a steerable catheter to the level of the tricuspid annulus. Central annular location and annular axiality are confirmed via imaging. The grasping legs of the ventricular stent are then exposed, and the device advanced into the RV. The device is then withdrawn towards the RA to capture the native leaflets between the grasping legs and annulus. 3D MPR imaging is employed to ensure leaflet engagement by all grasping legs to achieve device stability and prevent paravalvular leak. 3D MPR assessment of grasping leg engagement is performed by placing the MPR crosshairs in the centre of the device at the level of the grasping leg tips and rotation of the MPR lines to sequentially assesses each grasping element. Device position and axiality is adjusted as required to achieve optimal leaflet capture. The atrial flange is then exposed, the valve fully exposed, and deployed.The Intrepid  system consists of a self-expanding implantable bioprosthesis, delivery system, and loading system. The bioprosthetic implant is composed of a 27 mm trileaflet bovine pericardial valve mounted on an inner nitinol stent, an outer nitinol fixation ring that engages the tricuspid annulus, and an echogenic woven polyester skirt that forms an atrial brim. Device fixation is achieved by small outer stent cleats that produce frictional engagement with the native valve leaflets, and by varying degrees of radial stiffness in the outer stent that create a cork-like confirmation effect around the tricuspid annulus. The device is available in 44 and 48 mm sizes and is delivered via femoral venous access through a 35 mm sheath. First in-human experience using the Intrepid valve for treatment of severe TR has been described and an early feasibility trial is currently underway (NCT04433065) –84.TEE and fluoroscopy are used to guide the delivery system to the tricuspid annulus and obtain central annular position perpendicular to the tricuspid annulus. Once satisfactory position has been achieved with the superior device capsule ∼2 cm above the tricuspid annulus, the system is pressurized to expand the atrial brim. Re-evaluation and positioning of the device guide by 3D MPR imaging and fluoroscopy is undertaken before the device is fully expanded and deployed. Valve hemodynamics, valvular and paravalvular regurgitation are assessed as per standard protocols.Percutaneous tricuspid annuloplasty devices reduce tricuspid annular diameter to improve leaflet coaptation and reduce TR. Annuloplasty procedures are best suited in cases of functional TR where annular dilation is the primary mechanism responsible for TR. Anatomic determinants of suitability for annuloplasty are outlined in The Cardioband tricuspid valve reconstruction system  is a transcatheter tricuspid annuloplasty device for the treatment of severe functional TR. The original device used in the early feasibility trial was composed of a contraction wire within a polyester fabric covering and radiopaque markers. The device has since been iterated, however, the mechanics of device implantation remains similar. Up to 17 individual anchors (prior device) or 14 individual anchors (current device) are implanted in the annulus avoiding the region of the triangle of Koch. After implantation, the contraction wire is cinched to reduce annular diameter and reduce TR. Results from the Edwards Cardioband Tricuspid Valve Reconstruction System Early Feasibility Study of 37 patients demonstrate 73.0% of patients achieved ≤ moderate TR at one year, with significant reduction in tricuspid annular diameter and RV end diastolic volume .en face tricuspid annulus are established to assess device trajectory and axiality with the annulus. The delivery system is advanced to the right atrium and position above the anterior-septal commissure (prior device) or posterior-septal commissure (current device) with position confirmed on 3D TEE. Each anchor is delivered just outside the leaflet hinge point and stability is confirmed with a push pull test assessed with fluoroscopy and TEE. After the final anchor is deployed, the Cardioband is then cinched to reduce annular diameter under continuous TEE assessment and adjusted to achieve the optimum hemodynamic result.Procedural imaging guidance is performed using fluoroscopy and TEE. RCA angiography is performed, and a guidewire is passed into the RCA, prior to commencing the procedure. Fluoroscopic projections of the RV long axis perpendicular to the tricuspid annular plane and of the The Tri-Ring annuloplasty system  is an adjustable transcatheter annuloplasty ring implanted through a two-stage process. The ring is introduced via 22Fr transjugular access by a delivery system containing a balloon expandable scaffold. The ring is circumferentially attached to the tricuspid annulus by a series of small barbs. The ring is left in place for 90 days during which time tissue growth surrounding the barbs firmly secures the ring to the tricuspid annulus. The ring is then tightened using a 26Fr adjustment tool to reduce annular diameter and improve leaflet coaptation. First in-human experience with the Tri-Ring system has been described and the Early Feasibility Study of the Cardiac Implants Percutaneous Ring Annuloplasty System for the Treatment of Functional Tricuspid Regurgitation trial is currently underway (NCT04890821) .Procedural imaging guidance is performed with fluoroscopy and TEE. The delivery system is advanced to the RA and the ring expanded to a round circular shape via the balloon expandable delivery scaffold. The ring is maneuvered to the central annulus and annular axiality established. The ring is attached to the annulus via the anchoring barbs. The delivery the system is collapsed and removed from the body. A thin tether remains attached to the ring and is burrowed in a temporary pouch under the skin. After ∼90 days and adequate tissue growth has covered and stabilized the ring, the adjustment tool is advanced over the tether and pulled, cinching the tricuspid annulus. Cinching is performed under continuous TEE assessment to achieve an optimal hemodynamic result. Finally, the implant tether is secured, and the adjustment tool removed.Heterotopic TV replacement has been demonstrated to reduce symptoms of congestion in patients with symptomatic severe TR. The efficacy of this therapy for RV remodelling, however, is unclear. The anatomic determinants of suitability for this procedure are displayed in The TricValve  system is a dedicated bicaval therapy for treatment of severe TR. The system comprises of two different, self-expanding nitinol stents harbouring pericardial leaflets, designed specifically for the anatomic characteristics of the superior vena cava (SVC) and IVC. The SVC stent is contoured with a high radial force “belly” and a long skirt for device fixation and prevention of paravalvular regurgitation. The IVC stent has high proximal radial force for stent fixation at the RA/IVC junction and a short skirt so as not to impede hepatic venous return. Both stents are delivered via femoral venous access using a 27.5Fr delivery system. Multiple sizes for the IVC and SVC stents are available. Results from the TRICUS-EURO study, a single arm observational study of 35 patients, demonstrate excellent procedural efficacy and safety, and significant improvement in quality of life and NYHA classification at 6 month follow up. No significant improvement in hemodynamic parameters or RV volumes, however, were observed following treatment , 87.Baseline transthoracic echocardiography (TTE) should be performed for screening of exclusion criteria . Device sizing and anatomical suitability is assessed with CT. For the SVC stent, evaluation of the diameter at the superior cavo-atrial junction, level of the PA, confluence of the innominate trunk, and distance between these points, is required. A minimum distance of 50 mm between the superior cavo-atrial junction and innominate confluence is required to accommodate the SVC stent. For the IVC stent, assessment of the inferior cavo-atrial junction, IVC diameters above and below the hepatic veins, and distance between the hepatic veins and RA is required. A short distance between the hepatic veins and RA and acute angulation of the cavo-atrial junction are unfavorable characteristics that may compromise device stability and predispose to paravalvular regurgitation.Deployment of the SVC stent is guided by fluoroscopy alone. After establishing femoral venous access, a Swan-Ganz catheter is placed in the right PA and a pigtail placed in the SVC. An SVC angiogram is performed to identify anatomical landmarks and establish a roadmap for deployment. The device is deployed from cranio-caudal direction. Ideal placement is with the broadest section of the “belly” at the level of the right PA catheter. For the IVC stent, a venogram of the IVC, including the inferior cavo-atrial juncture, serves as a guide for deployment. Ideal deployment of the IVC stent is with 5–12 mm of the proximal stent strut into the RA. TTE or TEE are useful adjuncts for IVC stent positioning as both readily image the inferior cavo-atrial junction and can be used to evaluate stent height and paravalvular regurgitation. Both the SVC and IVC stents are recapturable up to 80% deployment.The TRICENTO system  is a self-expanding bicaval stent graft for treatment of severe TR. The system is composed of a self-expanding nitinol frame lined with porcine pericardium with a lateral bicuspid valve that faces the RA and prevents systolic backflow. The device is delivered via the right femoral vein through a 24Fr sheath. The device is custom fabricated to individual patient specifications. Retrospective registry experience of 21 patients demonstrates excellent procedural safety and improved NYHA functional class with reduction in congestive symptoms at 6 month follow up. In a subset of 7 patients that underwent CMR follow up, a mean reduction in RV end diastolic volume of 12% was observed .Dimensions for device fabrication are derived from CT . Sizing The device is deployed under fluoroscopic guidance. TEE may be used as an adjunct, however, is not mandatory. Right ventriculography and SVC angiography are performed to identify anatomic landmarks. The device is introduced via right femoral access and then deployed craniocaudally from the SVC, through the RA, and into the IVC. Radio-opaque device markers are used to guide device orientation. The device is re-sheathable up to 90% deployment. After deployment, right ventriculography and bicaval angiography are performed to evaluate continence of the valvular element and assess for endoleaks. Fusion imaging of echocardiographic and CT imaging with fluoroscopic projections has also been described to guide deployment , 89.The Mistral device  is a novel therapy for leaflet approximation and treatment of TR. The device consists of a spiral-shaped nitinol wire which achieves leaflet approximation through rotational grasping and approximation of the chordae tendinae. The device is delivered using an 8.5Fr steerable sheath via femoral venous access and is available in two sizes. Procedural imaging guidance is performed with fluoroscopy and TEE. After establishing access, the delivery catheter is advanced to the RA and the Mistral device is unsheathed to assume spiral configuration. The device is centred in the annulus, advanced into the RV, and maneuvered at the chordal level to the intended commissure for treatment. The device is rotated ∼5 times. Chordal engagement and device stability assessed with TEE and fluoroscopy. Evaluation for tricuspid stenosis and residual TR severity is performed before device release. Implant feasibility and reduction in TR has been demonstrated in the first in-human case series . The TRIThe Tripair device  is a transcatheter spacer device designed for treatment of functional TR. The device consists of a spacer balloon which crosses the tricuspid valve to seal gaps in leaflet coaptation attached to a self-expanding, crown shaped, right atrial frame which anchors the device in the right atrium. The device is delivered via an 18Fr steerable catheter via femoral venous access. The Tripair device is currently in pre-clinical testing .The Croívalve DUO Tricuspid Coaptation Valve system  is a novel transcatheter device for TV repair and replacement. The device is composed a coaptation valve which acts as a spacer to seal gaps in leaflet coaptation which contains a central valve to support diastolic flow. The device is anchored to a stent in the SVC via a support catheter which allows for respiratory and cardiac motion. The device is delivered via right internal jugular access. Procedural guidance is based on standard imaging with fluoroscopy and TEE . An earlIn the absence of robust data supporting the use of isolated TV surgery for symptomatic severe TR, as well as the high in-hospital mortality associated with surgical intervention, transcatheter tricuspid valve therapies are rapidly evolving. Multiple classes of therapeutic devices are currently in development. Some devices have a surgical predicate with data to help define appropriate clinical and anatomic patient populations for these novel devices. Other devices are completely novel in their approach to disease pathophysiology. However, the future of all these devices will be in large part be determined by safety and efficacy, with the expectation of lower procedural morbidity and mortality and improvements in long-term outcomes. Multi-modality imaging is currently the cornerstone of patient selection, device choice and procedural success. Advanced imaging tools for analysis of anatomic as well as hemodynamic suitability for TTVI have also advanced our understanding of the pathophysiology of TR. Intraprocedural imaging software and devices have been integral to the procedural success of transcatheter tricuspid valve therapies and helps drive the innovation around device development.


Marfan´s syndrome is a multisystemic, autosomal dominant congenital abnormality of variable penetrance that affects the integrity of connective tissue. In the cardiovascular system, the dysfunction of the physiology of the aortic root and the myocardial fibrosis originates non-ischemic cardiomyopathy independent of valve lesions. Few data have been reported on the prevalence of arrhythmias and its impact on heart function. We present a 21-year-old man with Marfan’s syndrome and heart failure with frequent supraventricular arrhythmias and aortic root dilation. After ablation in the posteroseptal area of the mitral ring and Tirone David Surgery, there was clinical improvement, the left ventricular ejection fraction increased dramatically from 33% to 46%, the left ventricular end-diastolic volume decreased from 90 ml/m Marfan syndrome (MSx) is a multisystemic, autosomal dominant congenital abnormality of variable penetrance that affects the integrity of connective tissue. The incidence is 1:5000 with no predilection for gender, ethnicity, or geographic distribution. It presents as a new mutation in 25% of cases, and in 90%of cases it is caused by mutations in the Fibrillin-1 gene (FBN1) located on chromosome 15Q21.1 2, eccentric hypertrophy, type I diastolic dysfunction with E/A ratio of 0.57 and E/e’ in 14, right ventricle of normal dimensions and function . There was left atrial dilatation with a volume of 40 ml/m2, aneurysmal dilatation of the ascending aorta (52 mm), no significant valvulopathies and no signs of pulmonary hypertension; it is very important to mention that the patient had a suboptimal sonographic window due to his thoracic anatomy. The tomographic study revealed a dilated aortic root . The patient was a 21-year-old man diagnosed with Marfan´s syndrome (MSx) at the age of 10. He was treated with 5 mg of nevibolol daily. The patient reported progressive shortness of breath and palpitations over 4 years that deteriorated to NYHA functional class III. Transtoracic echocardiography showed left ventricular systolic dysfunction with a left ventricular ejection fraction (LVEF) of 33%, left ventricular end-diastolic volume of 90 ml/mtic root . . The NT-proBNP was 1100 pg/mL. Unfortunately, cardiac magnetic resonance imaging was not performed because this method was not available in the hospital. As no cause of cardiomyopathy apart from MSx and supraventricular arrhythmias was found, an electrophysiological study and ablation of the arrhythmogenic focus was pursued. Ablation was performed with radiofrequency at the level of the posteroseptal region of the mitral ring . Three months later, the heart team decided to replace the aorta with a dacron tube (Tirone David surgery) without complications. Twenty-four-hour electrocardiographic monitoring revealed frequent supraventricular premature atrial complexes (PACs) around 27% of total beats, and five episodes of atrial tachycardia at 150 bpm . The NT-ral ring . Three m2, normal diastolic function with E/A ratio of 1.5, E/e´ in 11 and mild dilatation of the LA (diameter 40 mm/m2). The NT-proBNP control was 180 pg/mL. After the aforementioned procedures, the patient reported considerable clinical improvement and functional capacity NYHA I. The 24-hour electrocardiographic monitoring showed a decrease in the frequency of PACs to 2.3%. Echocardiographic evaluation 8 months after the ablation showed improvement of the LVEF to 46%, left ventricular end-diastolic volume of 77 ml/m-Arrhythmia-induced cardiomyopathy is a ventricular condition caused by a persistent arrhythmia involving irregular, asynchronous, and/or rapid contractions that produce hemodynamic, electrical, and structural changes and neurohormonal activation Fatima Ezzedine et al. assessed the prevalence of arrhythmias in 213 patients with MSx. They concluded that atrial arrhythmias occurred in 16% of them, and 95% of these were atrial fibrillation, 3% atrial flutter, and 3% paroxysmal supraventricular tachycardia. Ventricular tachycardias were detected in 5% In a study of 846 patients, Sampath Gunda et al. found no association between PACs and cardiomyopathy and suggested that irregularity and post-extrasystolic potential produced by PACs and PVCs played no pathophysiological role in cardiomyopathy. However, these findings cannot be generalized given that the patients had short-term follow-ups and only 62 patients had > 5% PACs In conclusion, we present the case of a patient with MSx in whom two important components that contributed to heart failure were identified: the first was the high frequency of supraventricular extrasystoles with episodes of atrial tachycardia, and the second was the dysfunction of the physiology and dynamics of the aortic root due to its dilatation. Ablation of the arrhythmogenic focus and Tirone David surgery were performed; both procedures contributed to the clinical and quality of life improvement of the patient, and could also be demonstrated by the echocardiographic and laboratory control.


Little is known about the clinical prognosis of gasdermin D (GSDMD) in patients with ST-elevation myocardial infarction (STEMI). The purpose of this study was to investigate the association of GSDMD with microvascular injury, infarction size (IS), left ventricular ejection fraction (LVEF), and major adverse cardiac events (MACEs), in STEMI patients with primary percutaneous coronary intervention (pPCI).We retrospectively analyzed 120 prospectively enrolled STEMI patients  treated with pPCI between 2020 and 2021 who underwent serum GSDMD assessment and cardiac magnetic resonance (CMR) within 48 h post-reperfusion; CMR was also performed at one year follow-up.P = 0.003; 31% vs. 13%, P = 0.02, respectively), as well as with a lower LVEF both in the acute phase after infarction  and in the chronic phase , larger IS in the acute  and in the chronic phases , and larger left ventricular volumes  by CMR. Univariable and multivariable Cox regression analysis results showed that patients with GSDMD concentrations ≧ median (13 ng/L) had a higher incidence of MACE (P < 0.05).Microvascular obstruction was observed in 37 patients (31%). GSDMD concentrations ≧ median (13 ng/L) in patients were associated with a higher risk of microvascular obstruction and IMH , which is a powerful MACE predictor. Nevertheless, the therapeutic implications of this relation need further research. AlthougGasdermin D (GSDMD) was recently identified as a mediator of pyroptosis-inflammatory cell death triggered by cytosolic sensing of invasive infection and danger signals , 8. UponCardiac magnetic resonance (CMR) imaging has been increasingly used for assessment of myocardial function, myocardial edema, infarction size (IS), and microvascular damage with high accuracy and within a single examination . The recIn the present work, CMR was used to confirm the presence of MVO and IMH, and to study myocardial function, IS, left ventricular volume. The objective of this study was to investigate the association between GSDMD in serum post-reperfusion and microvascular injury confirmed by CMR, and investigate the prognostic value of GSDMD as well as CMR parameters in post-reperfusion STEMI patients.2.2.1.2, and contraindications to CMR . Blood samples of GSDMD, CRP, IL-6, and IL-1β were obtained via peripheral venipuncture 24 ± 12 h post-PCI. All patients gave informed written consent to study protocols approved by the ethics committee of our hospital.The present study is a retrospective, observational analysis of 120 consecutive STEMI patients enrolled between June 2020 and May 2021 in Henan Provincial People's Hospital. The follow-up duration was one year. All patients had been treated with pPCI within 12 h after symptoms onset and had undergone CMR in the early post-infarction phase (within two days from symptoms onset). Exclusion criteria were chronic MI, acute myocarditis, Killip-IV heart failure, an estimated glomerular filtration rate <30 ml/min/1.73 m2.2.All patients were enrolled between June 2020 and May 2021 and were followed up until the time to an event or, in the case of no event, April 2022.The primary clinical endpoint [major adverse cardiac events (MACE)] was defined as a composite of all cause death, non-fatal reinfarction, the occurrence of new heart failure and stroke , 19. Add2.3.GSDMD (ab272463) ELISA kits were purchased from Abcam . The concentration of cytokines was measured by the ELISA kits according to the manufacturers' instructions. The results were normalized by volume for serum samples. All samples were tested at least in triplicate.2.4.t-test and the Wilcoxon-Mann-Whitney U-test. Proportions were compared by chi-square test or by Fisher's exact test, as appropriate. The association of GSDMD with LVEF, IS, and microvascular injury (MVO and IMH) was evaluated in linear as well as binary multivariable regression analyses as indicated. For binary logistic regression analysis, LVEF and IS were dichotomized by clinical established cut-off values  MACE-free survival was estimated and depicted by the Kaplan-Meier method. GSDMD as continuous variable was dichotomized for low concentration and high concentration before log-rank test by using optimal cutoff values determined by ROC curve. To guarantee prognostic value of GSDMD for STEMI patients. Univariable and multivariable regression models were developed to investigate the potential independent association between MVO and MACE-free survival. To disclose independent predictors of MACE, all inflammatory biomarkers and CMR parameters were included, GSDMD, IL-1β, IL-6, TNF-α, CRP, CtnI, age, smoking, diabetes, anterior infarct localization as calculated in univariable regression analysis, GSDMD, IL-1β, CtnI were entered in a multivariable regression model. CMR model included the major CMR prognosis markers  according to literature . Kolmogorov-Smirnov test was used to test whether the value comes from a normal distribution. The continuous data were expressed as mean ± SD and compared between groups by terature . Receive3.3.1.P = 0.001), had more often anterior infarction (P = 0.004), left anterior descending artery (LAD) as an infarction-related artery (P = 0.004), and TIMI flow 0 pre-pPCI (P < 0.001) occurred more often than in patients with GSDMD levels below the median.The baseline clinical characteristics of the classified based on a threshold of GSDMD concentrations (<13 ng/L vs. ≧13 ng/L) are presented in 3.2.P = 0.003; 31% vs. 13%, P = 0.02, respectively) was found in patients with high GSDMD concentrations (≧13 ng/L). Furthermore, patients with high GSDMD concentrations (≧13 ng/L) showed a lower LVEF both in the acute phase after infarction  (P < 0.001). Patients presenting GSDMD concentrations ≧ median also were significantly associated with larger IS in the acute  and in the chronic phases  (P = 0.005) as well as LVEDV  (Baseline CMR characteristics and their relationship with GSDMD levels are presented in < 0.001)  and in t< 0.001) . In addi= 0.003) .P < 0.001), IS , MVO , and IMH . Four models were evaluated where either baseline LVEF, IS, MVO or IMH were regarded as the dependent variable, and GSDMD, IL-1β, CtnI, diabetes, CRP and anterior infarction localization as independent variables. In all four models, plasma GSDMD levels were significantly correlated with LVEF , IS , MVO  as well as IMH , MVO , and IMH .In binary logistic regression analysis, GSDMD emerged as independent predictor of baseline LVEF   . However = 0.02) . Kaplan- points] . After aP = 0.0001). Furthermore, for the prediction of MACE, a cut-off value of 13.835 was set for risk assessment. Patients having high GSDMD concentration showed a significantly higher MACE-free survival, as determined by Kaplan-Meier curve analysis . In univariable analysis, presence of MVO, presence of IMH, IS, LVEF, EDV and ESV were significantly associated with the occurrence of MACE . In the multivariable Cox regression analysis, the presence of MVO and IMH were independent predictors of a higher incidence of MACE   .4.The main findings of our study were as follows: (1) The increased levels of the GSDMD in serum were associated with failed microvascular reperfusion (including MVO and IMH), larger IS, and worse myocardial function; (2) MVO and IMH were independently associated with MACE at one-year post-STEMI. The significant association persisted after adjustment for potential biomarkers, such as IL-6, IL-1β, CRP; (3) Higher levels of circulating GSDMD were associated with a higher incidence of MVO and IMH and lower MACE-free survival. Therefore, GSDMD has a promising role for GSDMD as a prognostic biomarker for more serious outcomes in the early post-STEMI phase and could also serve as a potential target for future clinical cardio-protection trials.While the timely restoration of the epicardial coronary artery to the ischemic myocardium by PCI is the primary approach to preserve myocardial viability, it also contributes to I/R injury not only to cardiomyocytes, but also to various myocardial components, including the microvasculature. The presence of MVO and IMH after STEMI is associated with a worse outcome . AccumulInflammation, traditional biomarkers such as C-reactive protein (CRP), Interleukin-6 (IL-6), and interleukin-1β (IL-1β), has been associated with cardiovascular events. IL-6 is an inflammatory cytokine that mediates both immune and inflammatory responses. A body of evidence previously highlighted that IL-6 increases substantially after AMI and is involved in the pathophysiological process of microvascular injury . ConsistPrevious studies indicated that CRP is the most extensively investigated inflammatory marker for coronary heart disease . Reindl High-sensitivity cardiac troponin I (hs-cTnI) assays have been recognized for improving diagnostic accuracy in the early detection of AMI and for their potential in risk stratification for patients with AMI. Previous studies demonstrate that risk assessment in STEMI patients could be improved by combination with cTnI . ConsistHowever, whether there are novel biomarkers should be explored. GSDMD mediated-pyroptosis act as a novel proinflammatory programmed cell death as well as release of proinflammatory cytokines IL-1β and IL-18 . HoweverIL-1β acts as pro-inflammatory multifunctional cytokine and is one of the main regulators following cardiovascular events. To investigate whether IL-1β is implicated in pathophysiology of microvascular dysfunction following myocardial reperfusion. The present study revealed that IL-1β is an important contributor of microvascular injury (MVO and IMH). Since GSDMD and IL-1β are closely related, it is important to evaluate whether GSDMD provides additional prognostic value above and beyond IL-1β. In our study, we emphasize the pivotal role of GSDMD in the acute setting post infarction since the association of GSDMD with microvascular injury remained independent even after adjustment for IL-1β.Accumulating evidence has revealed that the presence of microvascular injury (including MVO and IMH) and blood stasis adversely affects early left ventricular remodeling and are independently associated with adverse cardiovascular events , 28. RecClinical studies have also revealed that CMR can be applied as a tool for risk stratification and guide in the management of STEMI patients at risk of MACE , 32. In * values in the infarct region, suggesting that GSDMD may be involved in the pathophysiological processes of MVO or IMH, affecting the prognosis of post-reperfusion STEMI patients. In the present study, we confirm the prognostic significance of elevated GSDMD levels, which could have their potential application as a more precise risk marker for STEMI patients undergoing pPCI.Yet, the pathophysiological mechanisms of the relationship between MVO or IMH and worse outcome are not fully understood. Recent experimental and clinical studies have indicated the presence of a link between IMH and the persistence of inflammation , 33. In 4.1.The study population in this work was relatively small and the duration of the follow-up period was limited to one year after STEMI. Additionally, the number of the investigated events was relatively low. Furthermore, our data assessed the prognostic information of the presence of MVO and IMH but did not evaluate the extent of MVO and IMH. It would thus be important for future studies to elucidate the percentage of MVO in LV. CMR was performed on two days in STEMI patients who undergo pPCI. Yet, the IMH evaluation could have been affected due to its temporal variations in the few days after infarction.Serum GSDMD levels were measured once, within 48 h post-reperfusion, the median time of GSDMD measurement was 28 h. Therefore, the GSDMD release dynamics over time (pre- and post-PCI) and its potential prognostic information could not be provided. However, our other data suggest that the inflammatory factor IL-1β reaches its peak at 48 h post-reperfusion and this might be the optimal time point of measurement. Nevertheless, the optimal timing of GSDMD measurements remains unknown in our study and needs further research. Moreover, the promising gasdermins family (GSDMC and GSDME) was not investigated in the present study. Thus, future investigations are required to evaluate the association between GSDMC or GSDME and MVO or IMH in STEMI patients receiving pPCI.5.The increased serum levels of GSDMD measured at 48 h in STEMI patients treated with pPCI were independently associated with a higher MVO and IMH rates and larger myocardial injury as established by comprehensive CMR imaging. Moreover, the present results emphasize the value of GSDMD as a biomarker for risk stratification, which can serve as a potential therapeutic target for STEMI patients with microvascular post-reperfusion injury.


Subarachnoid hemorrhage is associated with high morbidity and mortality, and cerebral arterial vasospasm is one of its main complications that determines neurological prognosis. The use of intravenous milrinone is becoming more common in the treatment of vasospasm. This molecule has positive inotropic and vasodilating properties by inhibiting phosphodiesterase-3. Its most described side effects are cardiac arrhythmias and arterial hypotension. In this paper, we raise a new issue concerning milrinone and discuss an undescribed side effect of this treatment, left ventricular outflow tract obstruction (LVOTO). Dynamic LVOTO is a clinical situation favored by hypovolemia, decreased left ventricular afterload, and excessive inotropism that can lead to severe hemodynamic failure and pulmonary edema. To our knowledge, this is the first study describing milrinone-induced LVOTO. This could compromise cerebral perfusion and therefore the neurological prognosis of patients. While it is known that catecholamines may induce LVOTO, milrinone-induced LVOTO appears to be a new pathophysiological entity of which neurosurgical intensivists should be aware. Subarachnoid hemorrhage (SAH) by aneurysmal rupture accounts for 1% to 5% of all strokes . One of In this paper, we raise new issues concerning milrinone and report an undescribed side effect of this treatment that we observed in two patients hospitalized in a neurosurgical intensive care unit (ICU) for SAH : dynamic left ventricular outflow tract obstruction (LVOTO). This is characterized by a pressure gradient between the left ventricle and the aorta. The narrowed left ventricular outflow tract is the site of substantial flow, which can lead to anterior translation of the mitral valve (systolic anterior motion [SAM]) and regurgitation of the valve. Fixed LVOTO is due to particular anatomical conditions that can be corrected by surgery. Dynamic LVOTO is favored by the addition of predisposing factors . Clinically, LVOTO may induce hemodynamic failure up to shock, and neurosurgical intensivists should be aware of this complication of milrinone infusion.To our knowledge, we describe here the two first cases of LVOTO induced by milrinone.Informed consent was obtained from all individual patients described in this paper.This study has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. The Comité d'Ethique pour la Recherche sur Données Existantes et/ou hors loi Jardé (CERDE-HLJ) of the Rouen University Hospital provided the ethical approval (E2021-91).A 48-year-old male was admitted in a neurosurgical ICU for a Fisher 4 and World Federation of Neurosurgical Societies (WFNS) 1 SAH, by rupture of a right terminal and internal carotid aneurysm. His medical history included arterial hypertension, essential tremors, and active smoking. He had no cardiological follow-up and was not taking long-term medication. Cardiac auscultation was normal on admission. An emergency external ventricular drainage was performed to treat acute hydrocephalus followed by a radioembolization of the two aneurysms 24 hours after admission. Prophylactic treatment with nimodipine was administered orally. Faced with an unfavorable neurological evolution on the third day, with the appearance of aphasia and right hemineglect, another angio–computerized tomography (CT) was performed, showing a diffuse vasospasm. A treatment with intravenous milrinone was started, initially at an infusion rate of 0.5 μg per kg per minute and increased 2 hours later to 1 μg per kg per minute because of good hemodynamic tolerance. The introduction of milrinone was followed by a partial regression of aphasia, and nimodipine was maintained.Due to the reappearance of complete aphasia 7 days after ICU admission, the patient benefited from in situ dilatations of the anterior and posterior cerebral arteries for refractory vasospasm. This procedure was followed by a complete regression of neurological symptoms.Two weeks after ICU admission, while the patient was awake, extubated, apyretic, and hemodynamically stable without catecholamines, he presented a brutal hemodynamic failure with a systolic blood pressure inferior to 40 mmHg, with 120 bpm tachycardia and arterial oxygen desaturation up to 75%. A previously unknown systolic heart murmur was found. The patient remained fully conscious during this episode. He benefited from fluid therapy by 2 liters of crystalloids, orotracheal intubation due to respiratory failure, and norepinephrine infusion, which was rapidly increased at 2 μg per kg per minute. A transthoracic echocardiography was performed and showed an intraventricular gradient of obstruction, a hypercontractile left ventricle with telesystolic exclusion, and a grade 4 mitral regurgitation with SAM of the mitral valve. The interventricular septum thickness was normal, excluding ventricular hypertrophy, and cardiac ventricles were not dilated. Chest X-ray showed unilateral alveolar opacity of the left lung, consistent with an acute pulmonary edema . A chestStaphylococcus epidermidis meningitis on ventricular drain. Antibiotic therapy by linezolide was therefore started, and a change of ventricular drain was performed 48 hours after the initiation of antibiotic therapy.A 69-year-old patient was admitted in a neurosurgical ICU for a Fischer 4 and WFNS 4 SAH secondary to a right giant carotid and ophthalmic aneurysm rupture. Her medical history included hypothyroidism and osteoporosis. She had no history of heart disease and had no regular cardiac follow-up. Cardiac auscultation was normal at admission. Neurological management was marked by an emergency external ventricular drainage to treat acute hydrocephalus, followed by radioembolization of the aneurysm and the initiation of nimodipine treatment. A follow-up cerebral angio-CT performed 7 days after ICU admission revealed diffuse cerebral vasospasm, which prompted the introduction of milrinone . One day later, the patient was febrile with an inflammatory syndrome leading to the diagnosis of a A systolic murmur was reported 3 days after milrinone initiation. It was midsystolic, heard in the second right intercostal space, intense, and radiating to the carotid arteries, strongly suggestive of aortic stenosis. The patient presented a stable hemodynamic state but a Glasgow Coma Score fluctuating between 12 and 15. Transthoracic echocardiography was performed at the onset of this heart murmur to look for a valvulopathy. The echocardiography revealed a gradient of left intraventricular obstruction with a maximum telesystolic peak measured at 54 mmHg  and a hyThe dynamic LVOTO phenomenon is secondary to a decreased preload and a decreased postload with increased inotropism thus reducing the telediastolic and telesystolic volumes of the left ventricle -16. ThesThe difference must be made between fixed LVOTO, due to underlying anatomical factors  that are sometimes correctable by surgery. In patients with hypertrophic obstructive cardiomyopathy (HOCM), the onset or aggravation of the stenosis may be seen during hypovolemia, vasodilatation, physical exertion, or dobutamine stress ultrasound -18. In pDiagnosis of LVOTO is difficult and can only be done with echocardiography. The diagnosis relies on the presence of an intraventricular pressure gradient (measured in continuous Doppler) with a velocity peak ≥1 m/s (or LVOTO pressure gradient at least 30 mmHg) or an anterior systolic movement of the large mitral valve, which is attracted into the left ventricle flushing chamber (SAM) ,17. A meThe main differential diagnosis in this context of SAH is neurogenic myocardial stunning. This occurs in the acute phase of SAH. Unlike LVOTO, beta receptor overstimulation results in myocardial sideration. The common feature of the two conditions is the worsening with the use of catecholamines.We did not find any study describing milrinone-induced dynamic LVOTO. When looking for studies dealing with hemodynamic effects of milrinone, several of them have described a decrease in systemic and pulmonary vascular resistance, an increase in cardiac index, an improvement in diastolic function, and a decrease in pulmonary capillary wedge pressure -29. OtheHowever, our cases showed the occurrence of LVOTO after milrinone infusion start in two patients without any cardiac disease before ICU admission. Indeed, in our first case, the only predisposing factor appeared to be a punctual bolus of milrinone, resulting in acute LVOTO with SAM, functional mitral insufficiency, and shock. Mitral regurgitation associated with LVOTO is most often eccentric and travels to the left pulmonary veins , resultiGiven our observations and on the basis of LVOTO pathophysiology, we think that milrinone, by combining a positive inotropic effect with a systemic arterial vasodilator effect, could be a molecule that strongly promotes the occurrence of LVOTO.Milrinone plays an important role in the treatment of cerebral vasospasm, and several neurosurgical ICU teams are using it for their patients with SAH. However, our reports and the analysis of the LVOTO pathophysiology suggest that in patients that are hypovolemic or septic, milrinone should probably be used with caution. The onset of LVOTO due to milrinone may be difficult to diagnose because of the lack of a specific clinical sign. However, its consequences are potentially serious since the occurrence of shock could worsen cerebral ischemia and neurological prognosis in patients already treated for arterial vasospasm. Echocardiography should probably be proposed early in patients with hemodynamic instability associated with milrinone. The use of echocardiography should probably be proposed in the presence of the aforementioned triggers or in case of hemodynamic instability in patients treated with milrinone. Prospective studies on a larger patient population are needed to determine the incidence of these disorders and their impact on the prognosis of patients treated for arterial vasospasm with milrinone.In patients with septic shock, LVOTO appears to be an independent risk factor for mortality . It therLVOTO is probably an underestimated clinical situation in neurosurgical ICU. It may occur in patients without any previous cardiac diseases, and its diagnosis relies on echocardiography. There are numerous triggering factors that are frequent in patients in the ICU and that cumulatively promote its occurrence. Milrinone, because of its positive inotropic effect and systemic arterial vasodilator effect, appears to be a molecule that may provide LVOTO. Further studies are needed to evaluate the incidence of dynamic LVOTO and its impact on the prognosis of patients with cerebral vasospasm treated with milrinone.


Left ventricle myocardium has a complex micro-architecture, which was revealed to consist of myocyte bundles arranged in a series of laminar sheetlets. Recent imaging studies demonstrated that these sheetlets re-orientated and likely slided over each other during the deformations between systole and diastole, and that sheetlet dynamics were altered during cardiomyopathy. However, the biomechanical effect of sheetlet sliding is not well-understood, which is the focus here. We conducted finite element simulations of the left ventricle (LV) coupled with a windkessel lumped parameter model to study sheetlet sliding, based on cardiac MRI of a healthy human subject, and modifications to account for hypertrophic and dilated geometric changes during cardiomyopathy remodeling. We modeled sheetlet sliding as a reduced shear stiffness in the sheet-normal direction and observed that (1) the diastolic sheetlet orientations must depart from alignment with the LV wall plane in order for sheetlet sliding to have an effect on cardiac function, that (2) sheetlet sliding modestly aided cardiac function of the healthy and dilated hearts, in terms of ejection fraction, stroke volume, and systolic pressure generation, but its effects were amplified during hypertrophic cardiomyopathy and diminished during dilated cardiomyopathy due to both sheetlet angle configuration and geometry, and that (3) where sheetlet sliding aided cardiac function, it increased tissue stresses, particularly in the myofibre direction. We speculate that sheetlet sliding is a tissue architectural adaptation to allow easier deformations of the LV walls so that LV wall stiffness will not hinder function, and to provide a balance between function and tissue stresses. A limitation here is that sheetlet sliding is modeled as a simple reduction in shear stiffness, without consideration of micro-scale sheetlet mechanics and dynamics.The online version contains supplementary material available at 10.1007/s10237-023-01721-6. The left ventricular (LV) myocardium has a complex and well-organized microstructure. Investigation of LV tissue revealed that it has transmurally  varying myocyte orientation with an average angle close to 0°  simulations of the LV myocardium, to provide additional evidence for sheetlet sliding, and using reduced shear stiffness to model sheetlet sliding, investigate its effects on cardiac function and tissue stresses in healthy, HCM and DCM LV geometries. Finite element method (FEM) has in the past been very successful at revealing biomechanics details in health and disease , while smoothing was performed with Geomagic Studio . The healthy LV model was later morphed to one with concentric hypertrophy and one with dilated eccentric hypertrophy, to investigate biomechanics during such LV geometry alternations. Concentric hypertrophy was modeled as a 100% increase in wall thickness on the load-free geometry, via an offset of the epicardium outwards, while dilation was modeled as an 80% increase in end-diastolic volume (EDV) without a change in wall thickness on the load-free geometry, via an offset of both the epicardium and endocardium outwards  was reconstructed from the cardiac magnetic resonance (CMR) imaging of a healthy adult human volunteer. The protocol was approved by the Surrey Research Ethics Committee (protocol 10/H0701/112), and informed consent was obtained from all participants. Segmentation and reconstruction were performed with VMTK , by minimizing the Lagrangian function detailed by Shavik et al.  spring constraint on the entire epicardial surface to emulate interactions with surrounding tissues to prevent the model from drifting away  and aortic valve and mitral valve resistances (Rao and Rmv), and arterial and venous compliances . Initial volumes of arterial and venous were tuned together with values of resistances and compliances to obtain the expected pressure–volume loop for the normal LV. Thereafter, the same lumped parameter model was used for other LV geometries and cardiac contractilities and passive stiffnesses. Details of the lumped parameter model parameters are given in the Appendix. FEM simulations were conducted for 10 cycles to allow the lumped parameter model to converge.A simplified windkessel lumped-parameter model was coupled to the LV FEM, as shown in Fig. ) and Green–Lagrange strain  onto the local longitudinal–circumferential plane and the circumferential axis  was defined as the angle between the projection of myocyte direction  direction and its projection on the local longitudinal–circumferential plane  was the angle between the sheetlet  was the angle between the projection of myocyte (F) direction on the local radial—circumferential plane and the circumferential axis Fig. . VendeliC = 100 Pa), and EF was reduced to 46.1% when contractility was reduced and passive stiffness was increased to more realistically reflect disease physiology (C = 300 Pa). For the dilated LV with associated sheetlet and helix angles adjustments, which represents DCM, EF was 43.2% when contractility and passive stiffness were maintained at that of the healthy LV (C = 100 Pa), but was reduced to 34.9% when contractility was reduced and stiffness increased (C = 200 Pa). These results demonstrate that FEM can be flexibly applied to emulate disease features.The pressure–volume (PV) loops of the FEM results are shown in Fig. We tested the effects of sheetlet sliding when diastolic sheetlet angle was 0mentclass2pt{minimResults showed that when diastolic sheetlet angle was 18In Fig. We further investigated how different helix angle configurations will impact the sheetlet sliding function, using the healthy and HCM LVs . Using the model of linear endo-to-epi helix angle variation, we investigated various cases of transmural helix angle difference (epi-to-endo difference in helix angle) and transmurally averaged helix angle. Results are shown in Fig. We performed sensitivity analysis to understand how LV geometry and physiological factors will affect the above sheetlet sliding effects, focusing on factors relevant to cardiomyopathy remodeling. Results are shown in Fig. Firstly, where only the LV geometry was changed, while all other physiological FE settings  were retained at healthy LV settings, the influence of sheetlet sliding on cardiac function was slightly improved in the HCM LV, where gradients of functional parameters versus Next, we analyzed HCM and DCM simulations where both LV geometry and physiological FE settings were tuned to disease conditions. We observed that DCM simulations with diseased FE settings did not have significant difference from DCM simulations with healthy FE settings. This suggested that in DCM, LV geometry was the dominant factor determining the reduced effects of sheetlet sliding, rather than physiological factors.On the other hand, for HCM simulations with diseased FE settings, the influence of sheetlet sliding on cardiac function was significantly increased. For example, the stroke volume versus We further noted that the changing sheetlet angle from 18° to 48° increased gradients , the more advantages sheetlet sliding can provide. This was likely because the usual myocardial deformations could not engage the sliding deformation if sheetlets that were perfectly aligned to the myocardial longitudinal–circumferential plane, leading to no advantage to function. With nonzero diastolic sheetlet angle, some components of the sheetlet sliding shear deformation would contribute to longitudinal and circumferential strains (as can be shown with coordinate axes transformation), reducing the resistance of the myocardium to its cyclic deformations, and enhancing function. Theoretically, at the sheetlet angle of 45°, the maximum amount of sheetlet sliding shear deformation would be aligned with longitudinal/circumferential strains, and the effects of sheetlet sliding would be at its maximum.Our second observation was that sheetlet sliding has a stronger effect on cardiac function in the hypertrophied LV, a modest effect in the normal LV, and a weaker effect in the dilated LV. In the DCM LV, our results showed that it was the dilated geometry that inhibited sheetlet sliding effects. We speculate that this was due to the lower relative wall thickness  in dilated hearts, effectively representing an LV with thinner walls, leading to reduced influence of wall stiffness on cardiac function. The mechanism by which sheetlet sliding enabled better cardiac function was that it reduced shear stiffness in specific directions, thus reducing resistance to deformation. In DCM, where wall stiffness was not as important, it logically followed that sheetlet sliding effects are weaker.In the HCM LV, the hypertrophied LV had additional myocardial mass that led to a larger overall stiffness, which required increased energy burden to deform, thus causing increased resistance to deformation. Sheetlet sliding helped to reduce this deformational resistance and would thus have a stronger effect in HCM hearts. However, the most important factor that allowed strong sheetlet sliding mechanisms in HCM hearts was that the sheetlet angle was close to 45° , whereas Nielles-Vallespin et al. had measured sheetlet angle mobility to be 47° via DT-MRI . With our current approach, when the load-free geometry was loaded to the end-diastolic state, errors were approximately 3.2% for long axis length, 7.3% for wall thickness, and 0.7% for diameter. However, since our inflated geometry was still reasonable physiological, study conclusion should not be affected.Finally, the definition of the sheetlet angle was identical to its definition in the previous study Below is the link to the electronic supplementary material.


The average VE/VCO2 slope was 29.0 (5.3) and 16% (n = 11) of the patients had impaired ventilatory efficiency (VE/VCO2 > 34). In multivariable analysis, 3D GLS , age  and female gender  were independently associated with peak VO2. No association was found between left ventricle ejection fraction obtain and peak VO2 . Impaired myocardial deformation parameters evaluated by 3DSTE were associated with worse functional capacity assessed by peak VO2.Patients with hypertrophic cardiomyopathy may exhibit impaired functional capacity, associated with increased morbidity and mortality. Systolic function is one of the determinants of functional capacity. Early identification of systolic disfunction may identify patients at risk for adverse outcomes. Myocardial deformation parameters, derived from three-dimensional (3D) speckle-tracking echocardiography (3DSTE) are useful tools to assess left ventricular systolic function, and are often abnormal before a decline in ejection fraction is seen. The aim of this study was to evaluate the correlation between myocardial deformation parameters obtained by 3DSTE and functional capacity in patients with hypertrophic cardiomyopathy. Seventy-four hypertrophic cardiomyopathy adult patients were prospectively evaluated. All patients underwent a dedicated 2D and 3D echocardiographic examination and cardiopulmonary exercise testing (CPET). Values of 3D global radial (GRS), longitudinal (3DGLS) and circumferential strain (GCS) were overall reduced in our population: 99% (n = 73) of the patients had reduced GLS, 82% (n = 61) had reduced GRS and all patients had reduced GCS obtain by 3DSTE. Average peak VO Hypertrophic cardiomyopathy (HCM) is the most frequent genetic heart disease, with an approximate prevalence of 0.2% . It is cPatients with hypertrophic cardiomyopathy may exhibit reduced functional capacity, which is associated with increased morbidity and mortality. Progression to heart failure (HF) is a major concern in these patients and can be in part predicted by impaired functional capacity .The pathophysiology of reduced functional capacity in patients with HCM has been mainly linked to left ventricular diastolic and systolic disfunction, chronotropic incompetence and impaired stroke volume response .Cardiopulmonary exercise testing (CPET) is indicated by international guidelines as a safe and reliable test to characterize severity and mechanisms of functional limitation in patients with HCM. Reduced values of peak oxygen, ventilatory efficiency and anaerobic threshold are associated with progression to HF .Systolic function evaluation based on ejection fraction (EF) is not a sensitive method, since the former is typically normal or even increased in this group of patients. Myocardial deformation parameters derived from two-dimension (2D) and three-dimension (3D) speckle tracking echocardiography, on the other hand, are often abnormal before a decline in EF is seen .The heterogeneous LV hypertrophy and interstitial fibrosis that characterize HCM leads to variability in regional and global systolic and diastolic deformation parameters. Characterization and quantification of myocardial segmental and rotational mechanics by 2D and 3D speckle tracking echocardiography (3DSTE) is an evolving and promising technique [3DSTE provides a better quantification of cardiac chambers size and function, minimizing errors provoked by foreshortened views that can occur in standard 2D echocardiography .The aim of this study was to evaluate the association between myocardial deformation parameters obtained by 3DSTE and functional capacity in patients with hypertrophic cardiomyopathy.This prospective study included 74 HCM adult patients evaluated at the outpatient cardiomyopathy clinic at Hospital de Santa Marta, Centro Hospitalar Universitário de Lisboa and Hospital Garcia de Orta, Almada between December 2017 and August 2020.Diagnosis of HCM was made based on the European Society of Cardiology guidelines on Hypertrophic Cardiomyopathy . BrieflyPatients with LV ejection fraction < 50% and LV wall thinning were excluded. Epicardial coronary artery disease and previous septal reduction therapy were also exclusion criteria.Epicardial coronary artery disease was excluded by invasive coronary angiography or cardiac computerized tomography in symptomatic patients or asymptomatic patients older than 40 years.The investigation followed the principles outlined in the Declaration of Helsinki. All patients gave written consent.All patients underwent a dedicated 2D and 3D echocardiographic examination . LV morphology and function was assessed according to the recommendations of the American Society of Echocardiography . Evaluat2D global longitudinal strain (GLS) was used to evaluate LV myocardial deformation. Regarding 3D speckle-tracking echocardiography GLS, global circumferential strain (GCS) and global radial strain (GRS) were obtained.To perform 3D speckle tracking echocardiography (3DSTE) using the acquired full-volume 3D dataset of the left ventricle (LV), the 3D strain analysis software automatically detected the LV’s endocardial and epicardial borders, generating a precise 3D mesh model of the myocardium. Manual adjustments were made by experienced cardiologists. The software utilized “block matching” to compare 3D patterns of acoustic markers within regions of interest (ROIs), identifying and removing outliers. Spatial averaging was then performed for accurate strain analysis, calculating longitudinal, circumferential, and radial strain values for each LV segment throughout the cardiac cycle .2D GLS of -22.5 ± 2.7% was considered normal . Normal CPET was performed using a treadmill with the application of the modified Bruce protocol. The duration of the exercise was limited only by patients’ symptoms when reaching maximal effort.Ventilatory expired gas analysis was performed using Ergostik, Geratherm®, Cardio Solutions systems. The equipment was calibrated in a standard fashion before each test.A standard 12-lead electrocardiogram (ECG) monitoring, diastolic blood pressure (DBP) and systolic blood pressure (SBP), saturation probe and measure of expiratory gases were recorded.2), CO2 production (VCO2), minute ventilation (VE) and other CPET variables were acquired breath by breath.Oxygen consumption (VO2 (pVO2) was measured in each patient and reported as mL kg − 1 min − 1. The expected peak VO2 was calculated based on age, gender, and body index (adjusted for body mass/fat-free mass in obese patients) [Peak VOatients) .2 at peak exercise was used to obtain the ventilatory class. Anaerobic threshold was measured by V-slope method and by the analysis of ventilatory equivalents.VE/VCOData are expressed as mean and standard deviation (SD). The Spearman rank-order correlation coefficient was used to assessed univariable correlation between variables. Variables with significant correlations (p < 0.05) where analyzed using multivariable linear regression. Comparisons of groups were analyzed using 1-way analysis of variance (ANOVA) for parametric data or Kruskal-Wallis for non-parametric data. Analysis within groups was assessed by post-hoc Bonferroni test. A probability value of p < 0.05 was considered significant.Of 74 patients with HCM, mean age 56 15) years, 43 (58%) males, 40 patients (54%) were in New York Heart Association (NYHA) functional class I, 29 (39%) in class II and 5 (7%) in class III. Fifty-five patients (74%) had non obstructive HCM. Maximum LV wall thickness (MWT) was 20 (7) mm. Study population characteristics are shown in Table 5 years, Mean values of global longitudinal, radial, and circumferential strain are reported in Table Regarding the basal characteristics of our population, an association between NYHA class and 3D GLS was found (F 2.71) = 4.07; p = 0.02). Post hoc analysis with the Bonferroni test revealed that 3D GLS values were significantly lower in patients in NYHA III compared with patients in NYHA I , but not between patients in NYHA III compared to patients NYHA II   = 7.7; p = 0.001).1 = -0.14, 95%IC -0.35;0.06, p = 0.12; 3D GRS: β1 = -0.28, 95%IC -0.94;0.37, p = 0.39; 3D GCS: β1 = -0.10, 95%IC -0.45;0.25, p = 0.57), neither was left ventricular outflow tract obstruction .MWT was not related with 3DSTE strain measures (3D GLS: β2 was 21.01 (6.08) ml/Kg/min; 39 (58%) showed reduced exercise tolerance (predicted pVO2 < 80%) and 31 (42%) had a pVO2 < 20 ml/Kg/min. The average VE/VCO2 slope was 29 (5.3) and 11 (16%) of the patients had impaired ventilatory efficiency (VE/VCO2 > 34). CPET findings are shown in Table Regarding CPET findings respiratory exchange ratio was 1.03 (0.09) revealing adequate exercise effort. Mean time of exercise was 12.4 (4.3) minutes. Average pVO2 and gender (t (72) = 5.52, p < 0.01), pVO2 was higher in males – mean 24 (5.8) vs. 17 (5.3) ml/Kg/min than in females.There was an association between pVO2  and so did RV-RA peak velocity of tricuspid regurgitant jet , however no association was found after adjusting for baseline characteristics in multivariable analysis  .Regarding the echocardiographic findings, E/e’ showed a inverse relation with pVO2 and MWT  or between the presence of obstruction and pVO2 (t (-65) = − 1.11, p = 0.83).No association was found between pVO2. On the other hand, no correlation was found between LVEF  or GLS  obtained by 2D method and pVO2 .Univariable analysis revealed a correlation between 3D GRS , 3D GLS  and 3D GCS  with pVO1 = 0.1, 95%CI: 0.03;0.23, p = 0.014), age  and female gender  were independently associated with pVO2. The remaining 3D strain parameters (GRS and GCS) were not considered significantly related to pVO2 in multivariable analysis.In multivariable analysis, 3D GLS (β2, 3DGLS was also significantly decreased in patients with higher NYHA classes.In this study we found that that 3DGLS was independently associated with worse functional capacity determined by peak VOThe high variability of left ventricular hypertrophy and contractile capacity between different segments of the myocardium of a single HCM patient, makes 3DSTE a more sensitive method than 2D LVEF to characterize systolic function, considering its higher accuracy at assessing regional cardiac mechanisms. In our study we found a correlation between 3D evaluation of myocardial deformation and functional capacity, which could not be achieved with 2D LVEF.Overall strain parameters were reduced in our population, as expected for a cohort of HCM patients . Regardi2.As hypothesized, impaired myocardial deformation parameters evaluated by 3DSTE, namely 3D GLS, were associated with worse functional capacity objectively assessed by CPET parameters. On the other hand, there was not a significant correlation between LVEF or GLS obtain by 2D method and pVO2 in univariate analysis and were independently associated with pVO2 in multivariable analysis.Absolute values of 3D GLS showed the strongest correlation with pVO3D GLS was also significantly decreased from patients in NYHA class I to class III, which further confirms the association of this parameter with functional capacity. On the other hand, significant GLS variations between patients in NYHA class II and III could not be found. However, 2DGLS was also associated with NYHA class changes.3D speckle tracking echocardiography has been recognized has a useful tool in the global evaluation of HCM: some studies have reported its utility in predicting atrial fibrillation , family Incorporating 3DSTE in daily clinical practice can have positive prognostic implications in these patients, allowing for an early identification of patients with worse outcomes, facilitating more effective management strategies and timely interventions. Furthermore, prediction of functional capacity through 3DSTE can represent an alternative for patients who cannot undergo CPET.Our population showed reduced early diastolic mitral annular velocities measured using Doppler tissue imaging. Myocardial hypertrophy, ischemia secondary to coronary microvascular dysfunction and interstitial fibrosis causing chamber stiffness are responsible for impaired ventricular myocardial relaxation, largely described in patients with HCM , with coIn our cohort average E/e’ ratio correlated with functional capacity in univariate analysis. Unlike conventional Doppler indices alone, the transmitral E to e’ ratio has been particularly correlated with NYHA functional class in patients with HCM .2 were not significant when applied a multivariate analysis, which may indicate that other mechanisms such as reduced stroke volume response, ventilation/perfusion mismatch and abnormal peripheral oxygen utilisation may also influence exercise capacity [Exercise intolerance in patients with HCM can be, at least in part, attributed to raised left atrial pressures. However, the relation between average E/e’ and left atrium index volume and pVOcapacity .Controversy remains regarding left ventricular diastolic pressure and functional capacity at rest as major determinants of exercise capacity in patients with HCM, and more investigation is needed to clear the true mechanisms.The present work has some limitations. The sample size is relatively small, which may limit the generalisation of these findings and contributed for the absence of strong correlations in our analysis. Echocardiographic parameters were obtained at rest and not simultaneously with the physical effort.Impaired myocardial deformation parameter 3DGLS was independently associated with worse functional capacity assessed by CPET.Our study supports the emerging data about 3DSTE applications in HCM and its advantages over standard echocardiographic methods, namely in the evaluation of systolic function.