There is no formal diagnostic criterion for sepsis-induced cardiomyopathy (SICM), but left ventricular ejection fraction (LVEF) < 50% was the most commonly used standard. Tissue motion annular displacement (TMAD) is a novel speckle tracking indicator to quickly assess LV longitudinal systolic function. This study aimed to evaluate the feasibility and discriminatory value of TMAD for predicting SICM, as well as prognostic value of TMAD for mortality.We conducted a single-center retrospective observational study in patients with sepsis or septic shock who underwent echocardiography examination within the first 24 h after admission. Basic clinical information and conventional echocardiographic data, including mitral annular plane systolic excursion (MAPSE), were collected. Based on speckle tracking echocardiography (STE), global longitudinal strain (GLS) and TMAD were, respectively, performed offline. The parameters acquisition rate, inter- and intra-observer reliability, time consumed for measurement were assessed for the feasibility analysis. Areas under the receiver operating characteristic curves (AUROC) values were calculated to assess the discriminatory value of TMAD/GLS/MAPSE for predicting SICM, defined as LVEF < 50%. Kaplan–Meier survival curve analysis was performed according to the cutoff values in predicting SICM. Cox proportional hazards model was performed to determine the risk factors for 28d and in-hospital mortality.p < 0.05). According to the AUROC analysis, TMADMid presented an excellent discriminatory value for predicting SICM (AUROC > 0.9). Patients with lower TMADMid (< 9.75 mm) had significantly higher 28d and in-hospital mortality (both p < 0.05). The multivariate Cox proportional hazards model revealed that BMI and SOFA were the independent risk factors for 28d and in-hospital mortality in sepsis cases, but TMAD was not.A total of 143 patients were enrolled in this study. Compared with LVEF, GLS or MAPSE, TMAD exhibited the highest parameter acquisition rate, intra- and inter-observer reliability. The mean time for offline analyses with TMAD was significantly shorter than that with LVEF or GLS (STE-based TMAD is a novel and feasible technology with promising discriminatory value for predicting SICM with LVEF < 50%.The online version contains supplementary material available at 10.1186/s13054-022-04095-w. Sepsis-induced cardiomyopathy (SICM), initially described in the 1980s, is generally defined as an acute and reversible cardiac dysfunction that involves decreased left and/or right ventricular systolic and/or diastolic function, left ventricular dilatation, and absence of acute coronary syndrome –5 in mosEchocardiography is considered the most important method for the diagnosis of SICM. Every patient with unstable hemodynamics is suggested to receive echocardiography examination , 11. In LVEF and GLS measurements require a clear tracing of the endocardium; thus, high-quality echocardiographic imaging is essential. However, this is challenging because patients should be placed in the left lateral decubitus position (the routine ultrasound examination position). Ideal position is difficult to achieve for critically ill patients especially those with unstable hemodynamics, restriction due to surgical drainage tubes or organ support devices, such as continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO). Adequate image quality may also be challenging in patients with chronic obstructive pulmonary disease (COPD) or on positive pressure ventilation.Tissue motion annular displacement (TMAD) is a novel speckle tracking indicator that quickly assesses the LV longitudinal systolic function –20. TMADA single-center retrospective observational study was conducted in Zhongshan Hospital Fudan University. Patients who were admitted to the surgical intensive care unit (SICU) from March 2019 to July 2021 and met the following criteria were enrolled as study subjects: (1) age ≥ 18 years; (2) diagnosis of sepsis or septic shock; and (3) underwent echocardiography examination within the first 24 h after admission to SICU. Those who met any of the following criteria were excluded: (1) poor echocardiographic image quality or incomplete echocardiographic data; (2) incomplete clinical data; (3) history of valvular heart disease; (4) chronic heart failure (CHF) with the history of coronary artery disease (CAD), hypertrophic cardiomyopathy (HCM) or other ischemic heart diseases; (5) holder of cardiac implanted device; (6) atrial fibrillation; (7) refusal to participate in the study; and (8) loss to follow-up and fail to get consent. This project was approved by the Ethics Committee of the Zhongshan Hospital Fudan University . All participants or legal representatives were contacted through telephone calls and signed informed consent.Basic characteristic and clinical data from all participants were collected within the first 24 h after admission to SICU. Basic information was collected from the electronic medical record system, including age, gender, body mass index (BMI), comorbidity, medication history, septic source, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score and the Sequential Organ Failure Assessment (SOFA) score. Clinical information comprised heart rate, mean arterial pressure (MAP) and central venous pressure (CVP), cardiac troponin T (cTnT), N-terminal pro brain natriuretic peptide (NT-proBNP) and creatine kinase-MB (CK-MB).All conventional echocardiography examinations in our study were conducted using a CX50 CompactXtreme Ultrasound System  with a 1–5 MHz-phased array transducer. The recorded parameters included: left atrial dimension, LV end-systolic and end-diastolic volume (LVESV/LVEDV), LVEF, velocity–time integral of LV outflow tract (LVOT VTI), cardiac output (CO), early (E) and late (A) diastolic trans-mitral inflow velocity, early (e′) and late (a′) lateral diastolic mitral annular tissue velocity, maximal lateral systolic mitral annular tissue velocity (MA Smax), mitral annular plane systolic excursion (MAPSE), tricuspid annular plane systolic excursion (TAPSE), pulmonary arterial systolic pressure (PASP). LV volumes and LVEF were calculated by the modified biplanar Simpson method. E and A velocities were measured using pulsed wave (PW) Doppler at the tip of the mitral valve, and e′ and a′ tissue velocities were measured using PW tissue Doppler in the apical four-chamber view. E/A ratio and E/e′ ratios were calculated. LVEF < 50% was considered as the diagnostic criteria of SICM , 14.STE analysis was performed offline and averaged by two independent investigators who were trained by an echocardiography software engineer. During the echocardiographic analysis, the investigators were blinded to the patients’ clinical conditions. STE analysis was performed by the QLAB software, version 9.0 .To distinguish the different phases of the cardiac cycle, the opening and closing times of the mitral and aortic valves were derived from the electrocardiograph. For GLS evaluation, the semi-automated CMQ package of the QLAB software was used along the apical longitudinal axis of the left ventricle in four-, two-, and three-chamber views. When the system focused on two mitral annular and apical points of the three left ventricle longitudinal sections, the software automatically tracked the speckles of the endocardial border throughout the cardiac cycle. Any part of the myocardium that seemed imprecisely tracked was manually and carefully modified by the investigators. In each myocardial segment, the strain was measured, and GLS was calculated by averaging the peak strain values of the whole 17 segments during systole   were selected: the septal TMAD1) and lateral (TMAD2) areas of the mitral annulus, as well as the apex of the LV. The midpoint (TMADMid) between the two annuli ROIs was automatically detected after setting these three ROIs. Then, tracking was automatically performed frame by frame and the average of the base-to-apical displacement of the two mitral annulus ROIs was calculated in millimeters. TMADMid was also calculated in millimeters, and a percentage value of the midpoint displacement in relation to the total length of the left ventricle was calculated (%TMAD)  was reassessed by the same investigator with a minimum interval of 4 weeks from the first evaluation as the intra-observer variability. Then, to calculate inter-observer variability, the same 20 samples were examined by another investigator who was blinded to the results of the first investigator. Intra- and inter-observer agreement was evaluated using the intraclass correlation coefficient (ICC), which ranged from + 1 (100% agreement) to − 1 (100% disagreement). ICC scores of 0.75 or higher were considered as indicators of a quality control criterion with acceptable reliability. In addition, the duration of the LVEF, MAPSE, GLS and TMAD offline analyses, respectively, was also recorded for these 20 echocardiographic examinations.All patients were followed for 28 days after ICU admission or discharge, whichever occurred later. The primary outcomes of the study were the feasibility and discriminatory value of TMAD for SICM defined as LVEF < 50%. The secondary outcomes of the study were the feasibility and discriminatory value of MAPSE and GLS for SICM. The exploratory goal was to evaluate if TMAD, other echo or clinical variables had independent prognostic value for 28d or in-hospital mortality.p value < 0.05 was considered statistically significant.Continuous variables were presented as mean ± standard deviation (SD) or median and interquartile range, while categorical variables were expressed as frequency and percentage. For normally distributed continuous variables, comparisons were performed using the Student’s t-test, whereas non-normally distributed variables were analyzed with the Wilcoxon signed-rank test. Chi-squared test or Fisher’s exact test was used for categorical variables. The relationships between the selected variables were assessed by Pearson’s correlation analysis. The discriminatory values of TMAD, GLS and MAPSE for predicting SICM defined as LVEF < 50% were presented by the area under the receiver operating characteristic curves (AUROC). AUROC values were interpreted as follows: < 0.70 = poor; 0.70 to 0.80 = fair; 0.80 to 0.90 = good; > 0.90 = excellent. The optimal cutoff value of TMAD, GLS and MAPSE to discriminate SICM was determined according to the Youden index. Kaplan–Meier curves analysis with log-rank tests was performed according to the cutoff values of these echocardiographic parameters. Prognostic value of TMAD and other echo or clinical variables for 28d and in-hospital mortality were explored by Cox proportional hazard model analysis. All statistical analysis was conducted using SPSS 19.0 . The graphic presentation was created by GraphPad Prism 9.0 . A n = 87), incomplete echocardiographic data (n = 21), incomplete clinical data (n = 36), history of valvular heart disease (n = 22), CHF with history of CAD, HCM or other ischemic heart diseases (n = 20), holder of implanted devices (n = 12), atrial fibrillation (n = 10), refusal to participate (n = 4) and other reasons (n = 3). Finally, 143 patients were included. The flow diagram of the study is shown in Fig. From March 2019 to July 2021, 4865 critically ill adult patients were consecutively admitted to SICU, and 656 of them were diagnosed with sepsis. Among these patients, 358 completed echocardiography examinations within the first 24 h after admission to SICU. Of them, 215 patients were excluded mainly for the following reasons: poor echocardiographic image quality  or the non-SICM  group. No significant difference was found in age, gender, BMI, comorbidity, medication history and sepsis source between the SICM and non-SICM group. However, the APACHE II score and SOFA score of the SICM group were significantly higher than that of the non-SICM group . According to the laboratory results, patients in the SICM group had significantly higher cTnT, NT-proBNP and CK-MB within the first 24 h after admission, when compared to the non-SICM group . The 28d and in-hospital mortality were significantly higher in the SICM group than in the non-SICM group . Baseline and clinical information of the patients is summarized in Table According to the LVEF criteria, all patients enrolled were divided into the SICM n = 26, 8.2% or tp < 0.001).Among the 87 patients with poor echocardiographic image quality, 35 patients had inadequate imaging of the entire endocardium , and the other 52 patients had adequate imaging of the apex and mitral annulus but inadequate imaging of the other endocardium parts, especially the lateral wall of the LV  , but significantly shorter than that for LVEF or GLS .Intra- and inter-observer variabilities for LVEF, MAPSE, GLS and TMAD were assessed and are shown in Table p < 0.05). Meanwhile, LVESV and GLS in those with SICM were significantly higher than in non-SICM patients .Conventional and speckle tracking echocardiographic data of all patients are shown in Table p < 0.001)  Fig. .Fig. 4ReThe discriminatory values of TMAD, GLS and MAPSE for predicting SICM defined as LVEF < 50% were evaluated. The AUROC values of TMADMid, %TMAD, GLS and MAPSE were 0.902, 0.887, 0.938 and 0.812, respectively .Kaplan–Meier curves according to the cutoff values of each parameter were drawn Fig. . The resClinical and echocardiographic data of 28d and in-hospital survivors and non-survivors were collected and are shown in Table In this study, we found that TMAD was feasible in 84.8% of eligible patients, which is higher than GLS and LVEF. TMAD also presented higher intra- and inter-observer reliability and less time consumed for measurement. Compared with MAPSE, TMAD had higher discriminatory value for predicting SICM. Patients with lower TMADMid (< 9.75 mm) had significantly higher 28d and in-hospital mortality. BMI and SOFA were the independent risk factors for 28d and in-hospital mortality.Previous studies have demonstrated that LVEF decreased in patients with sepsis and the mortality of SICM patients was higher than those without SICM . ParadoxAs an indispensable hemodynamic diagnostic tool in the field of critical care medicine, echocardiography plays an important role in the evaluation of LV systolic and/or diastolic function, as well as in volume management. In recent years, there has been an increased interest in applying STE to evaluate the LV function in sepsis , 30–32. MAPSE is another simple, rapid and reliable method to assess LV longitudinal function, which has been shown to have good correlation with LV longitudinal strain in critically ill patients , 35. In The STE-based TMAD is a novel method for assessing LV longitudinal systolic function  and a teIn this work, four TMAD parameters were collected. Among them, TMADMid represented the midpoint displacement between TMAD1 and TMAD2, which better reflected the global systolic function of LV. Additionally, %TMAD represented the percentage value of TMADMid in relation to the total length of the LV and was supposed to reduce the bias caused by the different LV sizes in different individuals. According to the results, TMADMid and %TMAD exhibited good-to-excellent diagnostic accuracy for SICM, while TMADMid presented higher specificity and %TMAD presented higher sensitivity. We believe that TMAD had promising prospects for the diagnosis of SICM.Several limitations in this study should be considered. First, it was a retrospective single-center study with a relatively limited sample size. Several patients were excluded due to poor echocardiographic image quality or incomplete echocardiographic data, which might affect the results. Second, the possible effect of the annulus calcification on TMAD measurement was not assessed. Gökdeniz et al. found that GLS is correlated with the presence and severity of mitral annulus calcification . In our SICM is a common disease among septic patients and reports significantly high mortality. STE-based TMAD is a novel and feasible technique for discriminating SICM defined as LVEF < 50% in patients with sepsis.Additional file 1. TMAD measurement steps on the Qlab software. Open the Qlab software and select a clear echocardiographic image. Select TMAD package of the software and three ROIs: the septal (TMAD1) and lateral (TMAD1) mitral annulus, and the apex of the LV. The midpoint (TMADMid) of TMAD1 and TMAD2 is automatically detected. Then tracking will be automatically performed frame by frame and the results of TMAD1, TMAD2, TMADMid, and %TMAD are calculated (%TMAD).


Degenerative mitral regurgitation (DMR) based on posterior leaflet prolapse is the most frequent type of organic mitral valve disease and has proven to be durably repairable in most cases by chordal repair techniques either by conventional median sternotomy or by less invasive approaches both utilizing extracorporeal circulation and cardioplegic myocardial arrest. Recently, several novel transapical chordal repair techniques specifically targeting the posterior leaflet have been developed as a far less invasive and beating heart (off-pump) alternative to port-access mitral repair. In order to perform a safe and effective minimally invasive mitral chordal repair, thorough knowledge of the anatomy of the mitral valve apparatus and adequate use of multimodality imaging both pre- and intraoperatively are fundamental. In addition, comprehensive understanding of the available novel devices, their delivery systems and the individual procedural steps are required. Degenerative mitral regurgitation (DMR) is the second-most frequent valvular heart disease in Europe and the United States, affecting approximately 10% of the general population . DMR is In this review we focus on both the transapical approach of mitral valve repair using a novel chordal implantation HARPOON device, as well as on minimally invasive port-access mitral chordal repair. We will describe important anatomical considerations that are relevant for the procedure and offer a practical guide to periprocedural imaging.When a patient is opted for surgical correction of the mitral valve  a detailed evaluation of the MV must be available.The mitral annulus (MA) can be measured in parasternal long-axis (PLAX), apical four-chamber (AP4CH), apical two-chamber (AP2CH), and apical three-chamber (AP3CH) views. The measuring points should be located at the transition between the MV leaflets and the left atrium (LA). When the annulus is dilated, the anteroposterior (AP) diameter will predominantly increase, as represented in the PLAX, AP2CH, and AP3CH views. Special attention should be paid to mitral annular calcification (MAC), which—if present—can be seen in all MV views. However, MAC is especially well seen in the PSAX view .When the posterior leaflet base is displaced superiorly, mitral annular disjunction (MAD) could be present. MAD, characterized by a wide separation between the atrium-MV junction and the left ventricular (LV) attachment, can be detected both on TTE and TEE .The mitral leaflets can be adequately visualized in the PLAX and parasternal short-axis (PSAX) view and in the apical views. The PSAX view visualizes the surface of both leaflets and the closure-line can easily be followed from the anterolateral to the posteromedial commissure. The PLAX view cuts through the middle of the MV, thus picturing A2 and P2. In the AP4CH view the valve is transected in a more mediolateral manner, therefore visualizing A3 and P1. The A2 and P2 scallop are both visible In AP5CH, whereas AP2CH shows A1, P2, and P3. The PSAX view at the level of the MV is well suited for identification of clefts, which is especially relevant when the patient is scheduled for chord implantation .Prolapse of the MV is best identified in the AP3CH and PLAX views, because these transect the AP plane. An eccentric MR-jet is seen in case of significant prolapse, directed away from the prolapsing leaflet. Although 2D-images also enable identification of flail, it is hard distinguish the exact origin  on 2D-images. Therefore, supplementary TEE is valuable. In case of chordal rupture, an eccentric jet is classically seen from the flail leaflet toward the wall of the LA . RelevanIf a patient is accepted for chordal repair, it is useful to determine the leaflet-to-annulus index (LAI), defined as the ratio between the sum of anterior leaflet length and posterior leaflet length over anteroposterior length . As the 2 is representative for severe MR (or > 8 cm2 in TEE), as well as a jet-surface/LA-surface ratio of > 40%. Furthermore, Doppler evaluation of the pulmonary vein flow can be assessed in AP4CH or on TOE. When systolic backflow into one of the pulmonary veins is present, severe MR is likely (90% chance). Moreover, evaluation of the flow convergence zone on both TTE and TEE can attribute to the diagnosis of severe MR (in case of a radius > 0.9 cm). Other helpful complementary determinants in the diagnosis and evaluation of severe MR are increased mitral inflow velocity (>1.2 m/s) and enlargement of the LA and LV. Quantitative parameters that can be used for the evaluation of the severity of MR can be determined with the Proximal Isovelocity Surface Area (PISA) method  , the anterolateral and posteromedial commissures, the leaflet tips (corresponding to the line of each leaflet free edge), the posterior annular midpoint and the papillary muscle tips . Due to Minimally invasive MV repair (MIMVr) via a right anterolateral thoracotomy can be performed in the majority of patients with an indication for MV repair , as deteThe use of a combination of both computed tomography (CT) scanning of the total aorta and detailed echocardiography can add value to the pre-operative work-up.Although TTE is used to complete diagnosis in most patients, TEE is strongly recommended as it gives a clear image of the mechanisms contributing to MV disease and the specific site that causes MR. The presence of aortic regurgitation should be assessed on echocardiography preoperatively, as it can cause difficulties with cardioplegia administration . FurtherAs mentioned above, a detailed pre-operative analysis based on CT-scanning can add value both in determination of patient-eligibility and procedural planning of MIMVr. With visualization of the femoroiliac vessels on CT, the suitability for peripheral cannulation can be assessed. Kinking of these vessels and/or severe peripheral atherosclerosis or calcifications can specifically cause challenges for femoral cannulation. Moreover, arteries with a luminal diameter < 7 mm are poor candidates for cannulation. Therefore, minimal luminal diameter, atherosclerotic burden and tortuosity or abnormal angulation of femoroiliac vessels can be determined on CT . By visuIn the pre-operative work-up, the presence of severe mitral annular calcification should be evaluated (either on echocardiography or CT) as it is accompanied by high procedural risk, and extensive decalcification and reconstruction of the mitral annulus is very challenging through a minimally invasive approach .The position of the right hemidiaphragm can be analyzed both on CT  and chesAdditionally, CT-scanning can provide geometric and anatomical data on the mitral valve and subvalvular apparatus that can be taken into consideration in preprocedural planning. Complementary three-dimensional (3D) volume rendered images obtained from the preoperative CT scans may allow the surgeon to analyze the patient’s anatomy and determine optimal locations of port access, but are not often used in clinical practice for this purpose .In our high-volume MIMVr center, our main strategy to repair isolated prolapse of the pMVL is by the “respect” technique described by Patrick Perrier  in whichThe procedure is performed under general anesthesia with a double-lumen endotracheal tube. External defibrillator pads and meticulous control of activated clotting time (ACT) add to patient safety. The patient should be positioned in a 30* left lateral position with the right arm placed posteriorly . The rigA 4 cm right anterolateral mini-thoracotomy is made at the fourth intercostal space (ICS) to obtain surgical access. The location of the incision should be just inferolateral to the nipple in men and in the submammary crease in women. A more direct view of the MV can be achieved with a more lateral incision, but substantially increases the distance toward the MV . A closePeripheral cannulation is achieved through the femoral artery and vein and should be performed according to the Seldinger’s puncture technique. A 2–3 cm oblique incision is made in the groin. A purse-string suture with 5–0 Prolene is placed at the femoral artery and vein. The femoral vein is cannulated first and a 22 Fr long single venous cannula is inserted (in case of isolated MV surgery). The tip of the venous cannula must lie in the superior vena cava, or IVC with an additional cannula through the RIJV, especially for additional TV interventions. The location of the tip of the venous cannula should be confirmed on TEE. Hereafter, the femoral artery is cannulated with a 14–18 Fr arterial cannula  . The artA video-camera is placed through a 10 mm port in the 2nd or 3rd right ICS (at the right anterior axillary line) directly after accessing the thoracic cavity. A monitor that displays the procedural scopic images should be placed directly in front of the surgeon on the left side of the patient. Carbon dioxide should be delivered through the camera port into the surgical field.Pericardial stay sutures are placed and are brought out by an Endo-Close trocar site closure device (Medtronic) through a stab incision in the right sixth or seventh ICS. The pericardium should be opened 3–4 cm anterior and parallel to the phrenic nerve from the distal ascending aorta toward the diaphragm . ConsequA Chitwood aortic cross-clamp is placed across the ascending aorta through a 5 mm port in the 3rd right ICS to accomplish aortic occlusion. Alternatively, endo-clamping can be performed. By using a femoral arterial cannula with a side arm, a guidewire and hereafter multi-lumen catheter can be advanced into the ascending aorta under TEE guidance , 20. An A purse-string suture is placed for the cardioplegia needle vent with Prolene 4-0 RB. Antegrade crystalloid cardioplegia (approximately 2 L) is delivered directly into the aortic root through the cardioplegia needle. This should be repeated after 90–120 min if necessary. Body temperature should be around 34°C and vacuum-assisted venous drainage should be used throughout the procedure .A left atriotomy is performed with a paraseptal incision in the Sondergaard groove to access the MV and a left atrial roof retractor is placed to further expose the MV. The prolapse is corrected by implantation of expanded polytetrafluoroethylene (ePTFE) chords fixed to the fibrous tips of the appropriate papillary muscle complexes by a figure of eight (care should be taken not to transfer the midline). Following this, both strands of the chords are fixed to the prolapsing segment of the leaflet and the length is adjusted to correct the prolapse . This is repeated depending on the extent of the prolapsing segment, ensuring each 5 mm of prolapsing segment is secured by a chord on each lateral aspect. A water-test is used to fine-tune the length of the chords after which they are finally tied.An alternative approach is the implantation of ePTFE chords based on the “Loop technique” of von Oppell and Mohr . The reqImplantation of a semi-rigid annuloplasty ring as described by Carpentier , complemA water-test is conducted to immediately check the MV function after the repair is completed.The vent that is located in the right superior pulmonary vein should now be moved across the MV in order to divide the venting holes in both the LV and the LA. Subsequently, the LA is de-aired by filling it with saline during closure. When the absence of air is confirmed by TEE, the cardioplegia needle vent is removed during weaning of extracorporeal circulation (ECC).The LA is closed in two layers with a Prolene 3-0 suture. Temporary atrial pacemaker wires are placed.After completion of the repair, a TEE should be made intraoperatively to assess both the MV and left ventricular function (LVF). When assessing the MV function, the presence of residual MR, coaptation length, inflow-gradient and presence of systolic anterior motion (SAM) should be evaluated. In case of residual MR more than grade 1 (mild), and/or mean inflow-gradient > 5 mmHg and/or systolic anterior motion, a second pump run should be considered . FurtherThe pericardium is either approximated with a single suture or left open. Routine closure in layers is performed with a single small caliber left pleural drain (21 Fr).Several different strategies have been reported for the repair of prolapsing pMVL: more classic resection techniques that are based on the technique of Carpentier include triangular or quadrangular resection or plication, annular plication, leaflet sliding, and more recent implantation of ePTFE chords on the prolapsing segments. However, these techniques are always applied in combination with a (semi)rigid annuloplasty ring , 22, 23.p = 0.0007), equal survival and recurrence of moderate MR, when compared with resection  revealed that chord replacement was associated with a lower risk of reoperation  and orifice area  was observed in favor of chordal replacement (p = 0.03) and a larger effective orifice area of 1.86 ± 0.48 vs. 1.66 ± 0.47 cm2 (p < 0.001) in favor of chordal replacement. Importantly, Sakaguchi also demonstrated that the mean MR grade before discharge was significantly lower in the chordal replacement group than in the resection group , based on a combined amount of 291 patients who underwent elective MV repair for isolated pMVL prolapse between 2012 and 2020  at 1 year, 2.9% (1.6–4.2%) at 10 years and 4.2% (2.4–6.0%) at 20 years follow-up were reported by David et al. after correction of mitral prolapse with chordal replacement with or without leaflet resection in 746 patients . Another–1.4% at Event-free survival ranged from 97.7% (96.4–98.6%) at 1-year follow-up to 86.3% (83.4–88.8%) at 10 years and 62.9% (56.3–68.5%) at 20 years follow-up . SalvadoA recent study by Bonaros et al. revealed that based on a series of 686 patients with any mitral valve prolapse, the use of ePTFE chords to repair the prolapsing segment was an independent predictor of procedural success in MIMVr . SuccessAlthough the use of chordal implantation techniques widely increased over time in the setting of minimally invasive mitral repair, many studies do not isolate the experience with chordae in their reports as it is often part of a broad repertoire of MIMVr techniques .Out of all reports that have described the outcome of chord replacement for MIMVr, the group of Seeburger et al. has described the largest experience in three different reports –34. In 2In a study conducted by Kuntze et al., 632 patients underwent MVr with Gore-Tex loops for MV prolapse, of whom 522 patients underwent a mini-thoracotomy . Loops wAlthough the studies mentioned above are heterogeneous in composition of both the location of pathology and applied repair technique, it is safe to conclude that in the hands of an experienced MIMVr surgeon, artificial chordal implantation achieves a similar safety and efficacy outcome compared to conventional approach for mitral repair, while reducing surgical trauma .Beating Heart Mitral Valve Repair (BHMVR) is based on transesophageal echo-guided transapical implantation of artificial ePTFE chords on the beating heart for patients with severe degenerative mitral valve regurgitation (DMR) based on posterior mitral valve prolapse of the P2 scallop.This procedure allows minimally invasive surgical anatomical MV repair in patients with suitable anatomy. This technique limits risk and surgical trauma to a minimum, which shortens hospital stay and recovery after surgery. The Harpoon TSD-5  and the Neochord DS 1000  are the current available transapical chordal implantation systems that have gained Conformitié Européenne (CE) mark approval.Anatomic LV landmarks include the LV apex, left anterior descending (LAD) coronary artery and the diagonal branches. Due to the anatomical long axis of the (apex of the) LV and the location of the mitral valve, a direct left-ventricular approach via a small left antero-lateral thoracotomy provides sufficient exposure for transapical MV repair. Important considerations are extreme obesity and severe chest wall deformities, as these factors will impact exposure.We report the selection criteria based on the current practice as applied in our center . PatientOf note, patients are always prepared conform standard preoperative cardiac surgery work-up, including coronary angiography and laboratory work-up, according to the guidelines.We will describe the procedure step-by-step, based on the techniques as described by Gammie et al. , 37.The patient is prepared for a BHMVR with the Harpoon TSD-5  according to the hospital’s standard procedures. The procedure is performed under general anesthesia with a single-lumen endotracheal tube. A cell salvage system, standby cardiopulmonary bypass in case of conversion to port-access surgery, external defibrillator pads and meticulous control of activated clotting time (ACT) are added to enhance patient safety. A monitor that displays the procedural echocardiographic images is placed directly in front of the surgeon on the right side of the patient.Intraoperative TEE  is required throughout the entire procedure to guide the insertion of the introducer and delivery system, the subsequent steering and thereafter the deployment of the delivery system. Every procedure should therefore be conducted in close cooperation of a trained cardiothoracic surgeon and experienced imaging cardiologist.TEE assessment of the MV should be performed before insertion of the introducer, especially when the previous baseline TEE assessment was performed more than a month preoperatively. This enables identification of any changes in the MV pathology and the mechanism of MR and therefore any possible deviations from standard patient eligibility.The optimal intercostal space  is identified with the use of TTE. A small incision (approximately 5 cm) is made parallel to the rib in order to achieve a small left anterior  thoracotomy.A soft tissue retractor is recommended for use to avoid iatrogenic trauma due to rib spreading . After opening the pericardium, four pericardial stay-sutures need to be placed in the most medial and lateral parts of the thoracotomy, respectively, to ensure optimal exposure of the LV.The entry-location for the insertion of the introducer must be identified on the epicardium . This shAfter determining the entry-location, two concentric pledgeted Gore-Tex purse-string sutures should be placed in the myocardium. Note of caution: the use of Prolene 3-0 sutures is inadvisable, because of the risk of possible tearing of the crossing Gore-Tex sutures. At this moment, intravenous heparin should be administered to achieve an ACT above 350 s.The hemostatic introducer  is now ready to be inserted using a 0.035” guidewire. Insertion of the introducer should be visualized simultaneously in both the intercommissural and LAX views. On the mitral commissural view, the medial to lateral view of the mitral valve (P3-A3-A2-A1-P1) is seen from left to right. On the long-axis view, the posterior to anterior view (P2-A2) is visualized from left to right.The preloaded delivery system is inserted through the introducer. The delivery system is meant for single-use and has a 9-Fr external diameter (3 mm). During insertion  of the delivery system, hemostasis is maintained with the internal valve of the introducer , 37.At the moment of insertion, it is of great importance that the delivery system can be immediately located on TEE 2D images in bicommissural and long-axis views simultaneously at all times .In order to avoid transversing the native chordae tendinae of the aMVL, the delivery system should be first steered in the direction of the posterior leaflet after insertion.Guided by the instructions of the imaging cardiologist, the delivery system is steered and advanced toward the targeted location of the underside of the prolapsed segment of the pMVL. The ePTFE knots should be targeted close to the free edge of the pMVL and should be spaced 3–5 mm apart across the free edge of the prolapsed segment. The knots need to be placed sequentially from lateral to medial.When the delivery system has reached the targeted location, the atraumatic end effector on the distal tip of the delivery system should be used to stabilize the leaflet throughout the cardiac cycle on the underside of the pMVL at the targeted implantation site  37). A . A 37). After each deployment of the device, knot position should be checked with 3D  TEE view , visualiThe delivery system is withdrawn from the introducer after each deployment, leaving the two corresponding ePTFE strands exteriorized through the introducer lumen. In order to recognize the ePTFE strands from the following strands to the corresponding number of deployment, the end of the strands can be tied with the corresponding number of deployment (for recognition later in the procedure).A new delivery system needs to be inserted for each desired chord implantation. Usually three to five knots are implanted, with a minimum amount of three knots. After the final cord implantation has been performed, the introducer can be withdrawn from the LV. To imitate the final result on TEE, the ePTFE strands should be kept under tension.The purse-string sutures should then be tied and hemostasis needs to be achieved. Hereafter the ePTFE suture pairs are passed separately through a stiff pledget and then through a tourniquet. Under TEE guidance, all ePTFE sutures are tightened simultaneously, titrating the length of the implanted ePTFE chords based on optimal coaptation and minimal MR. Care should be taken that all the implanted chords are evenly tensioned, are not traversing any native chords of the aMVL or pMVL and most importantly are not too over-tensioned. Adequate coaptation (5 mm or more) should be created and residual MR > mild should not be accepted. When the optimal length of the ePTFE chords is achieved, the chords can be fixated with a clamp protected by rubber shuts. Each pair should then be tied over the pledget and cut distally.The pericardium is left open completely. Routine closure is achieved in layers and a single small caliber left pleural drain (21 Fr) is placed.Aspirin should be administered postoperatively and daily thereafter until 3 months postoperatively.So far, the results of two studies were published that have investigated the outcome of BHMVR with the HARPOON device in-human, including the Early Feasibility Study and the TRACER CE Mark Trial , 38. At 2 and a EuroSCORE II of 1.2 ± 1.1%  across both trials, which was defined by successful implantation of ≥ 1 ePTFE chords on the pMVL and demonstration of MR reduction from severe to moderate or less directly postoperatively and after 30 days. In total, two patients were converted to median sternotomy early in the study (study patient numbers 2 and 3) because of inadequate imaging equipment resulting in suboptimal artificial chordal placement. Another procedure was terminated directly after placement of the introducer due to high intra-cavitary LV pressures because of left ventricular outflow tract obstruction.The latest report of Gammie et al.  on the 1In treated patients, an average of 4.1 ± 1.0 pairs of ePTFE chords were implanted in the pMVL. Reported mean procedural time was 126 ± 36 min and the introducer remained in the left ventricle for 42 ± 18 min. Patients were discharged from the hospital after 6 ± 2.1 days.n = 1), recurrent MR due to ruptured ePTFE chords on postoperative day 211/253/352 (n = 3) and recurrent prolapse on day 279 due to invagination of the ventricular free wall below the pledget at the entrance site (n = 1)  were reoperated during 1-year follow-up. Reasons of reoperation were postoperative endocarditis ( (n = 1) . One pat (n = 1) . Causes  (n = 1) .p < 0.001) in the TRACER trial, but was not significantly reduced in the early feasibility study (43 ± 16–42 ± 20) (p < 0.001) in pooled data of both trials  by 11% (from 53 ± 5 mm to 47 ± 6) and a significant decrease of left ventricular end-diastolic volume (LVEDV) by 22% (from 153 ± 41 ml to 119 ± 28) at 1-year follow-up . The mea42 ± 20) , 38. A sh trials , and a mER trial . MV annuER trial .p < 0.001)]  and at a longer follow-up period 6 months postoperatively in the TRACER trial [from 106 ± 36 to 69 ± 24 ml at 6 months , sufficient mitral leaflet coaptation surface can be created after chordal placement in the P2 segment. Additionally, the AP diameter is also slightly reduced by this technique. Despite the fact that the durability of repair still has to be proven with future studies, the impact of this procedure is relatively low compared to on-pump mitral repair, especially in elderly patients.Minimally invasive MV repair of mid-segment pMVL prolapse by implantation of ePTFE artificial chords has proven to be a safe and equally durable repair technique as the classic (Carpentier-based) leaflet resection strategies by full median sternotomy, with the added value of less surgical trauma, improved cosmesis and faster postoperative recovery. Novel “least invasive” transapical transcatheter Beating Heart Mitral Repair technologies have the potential to provide an equally effective anatomical repair in selected patients with the added advantage of a real-time TEE-guided fine-tuning of the result on the beating heart. Whether or not the absence of an annuloplasty ring in selected patients with sufficient TGR will impact on mid to long term durability remains to be seen. Moreover, the reduced surgical trauma in this least invasive MVr technique should be weighted against the durability of the repair, which can be of value especially in elderly higher risk patients. Failure of the transapical BHMVR does not exclude the option of either redo BHMVR or port-access MV repair or replacement. In the end, it is all about weighing risks and benefits. Early results are promising, but long-term larger-scale studies—which are ongoing—are needed and eagerly awaited.All authors listed have made a substantial, direct, and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


N = 18 patients were enrolled. Tricuspid annulus S’ was abnormal in 16.7%, RV-longitudinal strain in 11.1%, tricuspid annular plane systolic excursion (TAPSE) in 11.1%, Tricuspid valve (TV) E/e’ in 33.3%, and TV E/A in 16.7%. The most prevalent combinations of pathological parameters were TV E/A + TV E/e’ and TAPSE + TV S’. With age, the probability of developing abnormal RV function increases according to age-dependent normative data. There is a significant correlation between TAPSE and mitral annular plane systolic excursion (MAPSE), and RV/LV-longitudinal strain (p ≤ 0.05). N = 5 individuals died 1.94 years (mean) after cardiac evaluation for this study, and all had abnormal RV functional parameters. (4) Conclusions: Signs of diastolic RV dysfunction can be found in up to one third of individuals, and systolic RV dysfunction in 16.7% of individuals in our cohort. RV function is impaired in PA patients with a poor outcome. RV functional parameters should be used to complement clinical and left ventricular echocardiographic findings.(1) Background: In propionic acidemia (PA), myocardial involvement often leads to progressive cardiac dysfunction of the left ventricle (LV). Cardiomyopathy (CM) is an important contributor to mortality. Although known to be of prognostic value in CM, there are no published data on right ventricular (RV) function in PA patients. (2) Methods: In this cross-sectional single-center study, systolic and diastolic RV function of PA patients was assessed by echocardiography, including frequency, onset, and combinations of echocardiographic parameters, as well as correlations to LV size and function. (3) Results:  Propionic acidemia (PA), a rare organic aciduria inherited in an autosomal recessive pattern, is caused by deficiency of mitochondrial propionyl-CoA carboxylase. PA affects around 1/100,000–1/250,000 individuals in most regions. Clinical presentation and disease onset vary depending on residual enzymatic activity, intake of propiogenic precursors, and the occurrence of catabolism. Most PA patients have an early onset of disease, with ketoacidosis and hyperammonemia in the first days of life, typically presenting as poor feeding, decreased arousal, and progressive encephalopathy after a symptom-free period. Late onset patients present after the neonatal period. Both early and late onset patients often develop various organ manifestations of this multisystem disease, including global developmental delay and intellectual disability, muscular hypotonia, movement disorders, seizures, pancreatitis, and cardiac disease. While PA can be identified through expanded newborn screening, most infants are diagnosed during the neonatal period based upon clinical suspicion and biochemical workup. Diagnosis is confirmed via molecular genetic testing  ,5,6,7,8.Cardiac disease is among the most prevalent organ manifestations in PA and a major contributor to mortality. It presents mainly as progressive left ventricular (LV) dysfunction, often leading to manifest cardiomyopathy (CM), with life-threatening acute heart failure during, e.g., metabolic decompensation and/or infections. Further, acquired long QT syndrome is described with potential occurrence of malignant ventricular arrhythmias ,5,6,7,8.CM is found in 9–40% in PA, usually diagnosed by conventional echocardiography . The treatment of cardiac disease consists of angiotensin converting enzyme inhibitors (ACE-I) and beta blockers, with anecdotal reports regarding Coenzyme Q10 ,6,7,8. In a recent study by our group, we found systolic and diastolic LV dysfunction in up to 72% of PA patients using advanced echocardiographic techniques .Interestingly, there are no published data on right ventricular (RV) functional parameters in PA patients. This may reflect that during routine echocardiographic evaluation of PA patients, sonographers mainly focus on assessment of LV function ,6,7,8. HDue to the complex RV anatomy, measuring RV function is, however, more challenging compared to assessing LV function. Furthermore, LV contraction contributes to RV contraction ,14. TherTo date, only data on LV functional parameters, mainly assessed by conventional echocardiography, have been published in PA. Therefore, we sought to investigate RV function in PA patients, including the impact of LV size and function on RV function, by advanced echocardiographic techniques.n = 18) were enrolled during the study period 2015–2020. The study individuals have been published before within a retrospective study on LV cardiac phenotype in PA [This is a cross-sectional single-center study with a prospective observational design conducted in a Tertiary Medical Care Center. Ethical approval (S-525/2010) was provided by the local Ethical Board. Written informed consent for all patients was obtained. All individuals with confirmed PA  by M-mode . RV fracAll results were compared to published age-dependent normative data ,23,25,26To test for intra- and interobserver variability, randomly selected cases were reanalyzed and calculated by the equation: Variability % = (m1 − m2)/(m1 + m2)/2 × 100%, where m1 and m2 are the mean values of the first and the second measurement sets of one investigator (intra-observation variability) or the first measurement set between two investigators (inter-observation variability), who were blinded to each other’s results. The variables tested were LVEDD, MAPSE, TAPSE, MV E, MV e’, TV E, and TV e’ .Statistical analyses were computed with R language version 4.2.0. The linear relationship between two numeric variables was computed via Pearson correlation coefficient. Frequent combinations of echocardiographic parameters were displayed as combination of two to a maximum of four pathological parameters, according to the ECLAT algorithm implemented in R package ‘arules’. The development of specific pathological echocardiographic functional parameters of the RV were modeled as left and right censored data with the ‘Surv’-function in package ‘survival’: if a pathologic functional parameter were found, this observation was treated as left censored, otherwise as right censored.n = 8 vs. male n = 10. Transthoracic echocardiography following a predefined protocol was performed during routine outpatient visits. None of the patients had structural heart disease . There were no cases of pulmonary hypertension. All patients had sinus rhythm during echocardiographic assessment, and none had acute preload changes. For further details regarding the study cohort, see reference [Eighteen patients were enrolled. The median age at visit for cardiac evaluation was 13.1 years (range 0.6–28.1 years). The gender distribution was female eference .RV and RA size, diameter, and anatomy of the tricuspid valve annulus were normal in all included patients. Inspiratory collapse of the inferior vena cava was ≥50% in all cases. None of the presented cases had signs of elevated pulmonary artery pressure . Tricuspid annulus S’ was abnormal in 16.7%, RV-strain in 11.1%, TAPSE in 11.1%, TV E/e’ in 33.3%, and TV E/A in 16.7%. Normal parameters were found in all individuals for RV-FAC, RV-MPI, and TV e’/a’ (TV e’/a’ assessed in adult patients). With growing age, the proportion of patients without abnormal RV function decreases a–e.N = 3 individuals  had a DCM with a LVEDD above the normal range and abnormal parameters for LV-FS, LV-EF, LV-MPI, and LV-GLS. Of these, n = 1 (ID 4) had additional abnormal RV-longitudinal strain, and another one (ID 14) had abnormal values for TAPSE, TV S’, and TV E/e’. The last one (ID 13) had no abnormal RV functional parameters. N = 1 individual (ID 9) had a dilated LV without pathological LV functional parameters; this patient also had normal values for all RV functional parameters. p ≤ 0.05). Correlation was more significant between LV functional parameters: LV-EF and LV-FS (p ≤ 0.001), LV-EF and LV-MPI (p ≤ 0.05), LV-FS and LV-MPI (p ≤ 0.01), LV-FS and MAPSE (p ≤ 0.01), and LV-MPI and MAPSE (p ≤ 0.05). Regarding the correlation of RV and LV function, there is a significant correlation between TAPSE and MAPSE, and RV longitudinal strain and LV-GLS  died  with a mean time distance of 1.94 years (range 0.4–3.6 years) after cardiac evaluation for this study. Death occurred at a median age of 18 years .Until publication of this study, Regarding RV functional parameters, ID 3 had pathological values for RV longitudinal strain, TAPSE, and TV S’. ID 4 had reduced RV longitudinal strain. ID 11 had abnormal TV E/A and TV E/e’. ID 14 had pathological TAPSE, TV S’, TV E/A, and TV E/e’. ID 15 had abnormal TV S’.In this study, we present novel data on systolic and diastolic RV function in PA patients. Up to one third of PA patients show signs of diastolic RV dysfunction, and 16% have systolic RV dysfunction, both in the absence of structural heart disease or pulmonary hypertension. With age, the probability of developing RV dysfunction, both diastolic and systolic, increases. Compared to our previous studies, RV dysfunction is less prevalent than LV dysfunction, which was found in up to 72% for both systolic and diastolic LV parameters in the same cohort.RV dysfunction is frequently described, although less compared to LV dysfunction, e.g., in long-term adult survivors of childhood lymphoma and acute lymphoblastic leukemia , hyperteAssessment of RV function should be considered important as it determines cardiac symptoms and exercise capacity in chronic heart failure, and it predicts the outcome in patients with DCM ,11,12,13Cardiac disease is associated with high morbidity and mortality in PA patients. Further, disease progression may not be haltered by conventional therapies such as ACE-I or beta blockers started once CM is detected by conventional echocardiography , raisingIn summary, in view of our current and previous data ,9 on carWith increasing age, PA patients are often noncooperative during echocardiography due to intellectual disability, and acoustic windows are hampered due to, e.g., immobility or scoliosis. We therefore (a) had to limit assessed echocardiographic parameters, and (b) quality of obtained views may have been impacted. However, intra- and interobserver variability for the echocardiographic parameters was excellent. There were no cardiac MRI or invasive data available, as not standardly recommended in PA. The strain algorithms used in QLAB have been validated for LV strain. However, algorithms used to determine strain are not chamber-specific, and, until 2018, both the apical four-chamber and the RV-focused four-chamber view were used to generate normal values for RV-GLS and FWS, and software packages designed for LV strain assessment were standardly used ,37,38. AWe present, for the first time in literature, data on RV function in PA. We show that assessment of systolic and diastolic RV function is feasible, and that diastolic RV dysfunction occurs in up to one third of individuals in our cohort, whereas systolic RV dysfunction is found in 16.7%. RV dysfunction is less prevalent than LV dysfunction, and there is some correlation between LV and RV functional parameters. LV and subsequent RV dysfunction was found in PA patients with a poor outcome. In summary, RV functional parameters can be used to complement clinical and LV echocardiographic findings in the assessment of PA patients. A possible prognostic role of RV dysfunction in PA remains to be investigated.


Thanks to the improvement in mitral regurgitation (MR) diagnostic and therapeutic management, with the introduction of minimally invasive techniques which have considerably reduced the individual surgical risk, the optimization of the timing for MR “open” or percutaneous surgical treatment has become a main concern which has highly raised scientific interest. In fact, the current indications for intervention in MR, especially in asymptomatic patients, rely on echocardiographic criteria with high severity cut-offs that are fulfilled only when not only mitral valve apparatus but also the cardiac chambers’ structure and function are severely impaired, which results in poor benefits for post-operative clinical outcome. This led to the need of new indices to redefine the optimal surgical timing in these patients. Speckle tracking echocardiography provides early markers of cardiac dysfunction due to subtle myocardial impairment; therefore, it could offer pivotal information in this setting. In fact, left ventricular and left atrial strains have already shown evidence about their usefulness in recognizing MR impact not only on symptoms and quality of life but also on cardiovascular events and new-onset atrial fibrillation in these patients. Moreover, right ventricular strain could be used to identify those patients with advanced cardiac damage and different grades of right ventricular dysfunction, which entails higher risks for cardiac surgery that could overweigh surgical benefits. This review aims to describe the importance of reconsidering the timing of intervention in MR and to analyze the potential additive value of speckle tracking echocardiography in this clinical setting. Primary mitral regurgitation (MR) is a degenerative disease involving the mitral valve (MV) with progressive worsening of severity and poor long-term prognosis if untreated, in terms of lower survival, impaired quality of life, and increased burden of atrial fibrillation (AF) and heart failure (HF) symptoms. The only effective treatment for severe primary MR is MV repair or replacement. For asymptomatic patients with primary MR, current indications for surgical treatment rely on bidimensional echocardiographic criteria.In fact, European and American guidelines , 2 recomOn the other hand, undertreated severe MR could lead to a chronic overload state which reflects first on the LA, then on pulmonary circulation and, consequently, on the right ventricle (RV). This chamber, being less muscular and strongly load- and LV function-dependent, is less capable to sustain hemodynamic overload for a long period; therefore, it is not uncommon that patients with severe MR present RV dysfunction. Studies have suggested how RV dysfunction, detected by noninvasive parameters as surrogate of pre-operative overall heart function, adds great value as a marker of poor post-operative outcome after MV surgery ; thus, iHowever, in the last years, the development of new minimally invasive surgery and percutaneous MV repair has considerably reduced surgical risks . CurrentThe aim of this review is to discuss the reasons for the potential need of introducing new echocardiographic indices to redefine the timing for MR surgery in light of the new evidence.The issue of MR surgical timing has been widely debated in the last decades .A previous study by Ling et al. has clearly shown how late surgery of primary MR is characterized by lower survival compared to patients undergoing the operation in presence of preserved LV ejection fraction (EF) and lower grades of symptoms . It is aTo date, none of the parameters used for surgical indications have a defined trend towards progression in the clinical history of patients with MR. In fact, some patients remain asymptomatic and stable for years, whereas others suddenly develop symptoms with or without the presence of echocardiographic criteria. For example, a recent study by Ma et al. showed that patients followed for around 4.5 years for MV prolapse having mild-to-moderate MR and normal EF. Among them, none of the patients with mild MR progressed to severe MR, whereas 50% with moderate MR progressed to severe MR, but no clinical variables or echocardiographic parameters predicted the progression of the disease apart from the dilatation of mitral annulus  .The absence of clear predictors of MR progression and clinical deterioration makes clinicians rely in favor of possibly misleading serial clinical and echocardiographic monitoring while on medical therapy, rather than expose the patient to surgical risks.However, in the last years, the advances in cardiac surgery and interventional cardiology have shown how the peri-operative risk can be reduced by the application of mini-invasive surgical techniques  and percMitraclip is currently the most studied, as it has shown satisfactory results for the treatment of primary and secondary MR , 14. TheThese data support the safety and effectiveness of MitraClip in primary MR, highlighting the importance of appropriate patient’s selection in order to improve peri-procedural results and reduce the subsequent rates of re-intervention. However, an early surgery, performed in patients with intermediate stages of chronic MR and without irreversible damage of MV anatomy and left cardiac chambers would probably lead to better results in terms of durability.p < 0.001) and a 71% decrease of HF risk  [Suri et al., with the development of a Mitral Regurgitation International Database, including more than one thousand patients with flail-related MV regurgitation and without class I criteria for surgery, have found that an early surgery (< 3 months from diagnosis) vs. medical treatment strongly influenced long-term survival , with a 53% reduction in 5-year mortality  over LV EF as an index of subclinical cardiac dysfunction in MR. Its use might lead to an improvement in the detection of LV damage in these patients as well as a more accurate prognostic evaluation for surgical referral.Kislitsina et al. demonstrated that preoperative strain measurements in 119 patients with degenerative MR undergoing surgical treatment represented the most accurate parameter in detecting an early LV dysfunction after MV surgery, despite preserved LV EF .n = 30/71 patients) or medical treatment and preserved LV EF undergoing exercise echocardiography, and to predict post-operative LV dysfunction [p < 0.001) [LV strain was able to identify subclinical LV dysfunction in asymptomatic patients with primary MR undergoing surgical  .n = 506) of patients with severe chronic MR, Kim et al. showed that LV GLS was a significant predictor of cardiac events  also with multivariate analysis, regardless of the presence of LV dysfunction, AF, and the type of surgery. Moreover, reduced GLS was also associated with all-cause mortality in this study  [.In a large cohort (= 0.040) .Another big study by Hiemstra et al.  conducteInterestingly, Singh et al. proved that, among patients referred for surgical treatment of severe MR, those with pre-operative preserved GLS had higher chances of postoperative LVEF > 50%, regardless of baseline LVEF also in MR of rheumatic etiology . Also, ATo conclude, a recent meta-analysis involving 2358 patients (from 8 studies) with severe MR and preserved LVEF highlighted that a reduced LV GLS before surgery was a predictor of worse postoperative survival  and LVEF .Table Even though its use could be still limited by the lack of disease-specific cut-off values and high dependence on acoustic window, LV GLS is a useful parameter to be included when considering early surgery in patients with severe mitral regurgitation and normal LVEF, providing important information on postoperative outcome.However, often LA strain is affected previously than LV strain Fig.  in patieLA strain is actually considered a hallmark of LV filling pressures and diastolic dysfunction , relatedPALS evaluation had a particular usefulness during pre-surgical evaluation of primary MR for the prediction of postoperative LA reverse remodeling and clinical outcome; in fact, PALS was independently associated to post-operative survival and functional capacity as assessed by NYHA class  and BorgNotably, LA strain has also shown a reliable index of LA remodeling following MitraClip procedure over conventional LV and LA echocardiographic indices .Moreover, PALS was the only resting echocardiographic parameter associated with exercise-induced pulmonary hypertension in a cohort of patients with asymptomatic MR . PALS duInterestingly, some authors focused on the potential relationship of LA strain with indications for MV surgery: Debonnaire et al. found a correlation between LA strain and current surgical criteria: symptoms, AF, and development of PH ; in patiDespite the occurrence of AF is considered a surgical criterion for MR, it is known that the development of AF is directly related to LA fibrosis ; therefoAll these findings suggest the potential value of considering LA strain as an additive criterion for the surgical referral of patients with primary MR. Table Logically, these promising results require larger studies to be generalized. Moreover, some limitations of LA strain by STE should be kept in mind. First, it strongly depends on loading conditions and image quality. Furthermore, the lack of disease-specific cut-off values for reference and the fact that a universally method of execution has not been reached yet should be considered. However, several documents have been published in order to standardize its application among different vendors and countries , 56.In patients with severe MR, the gradual increase in left heart filling pressure due to progressive LV and LA structural and functional damage leads to pulmonary circulation overload and development of pulmonary hypertension . The eler = −0.52; p = 0.02) and RV EF  in a subgroup of symptomatic subjects with degenerative MR, identifying a strict correspondence between the onset of symptoms and a state of pulmonary hypertension and biventricular dysfunction [This pathophysiologic picture describes patients with advanced stages of MV disease and coexisting biventricular failure. This was confirmed by Bakkestrom et al., who found a significant inverse correlation between resting mean pulmonary artery pressure (detected by right heart catheterization) and both LV EF  and to regurgitant volume  [p < 0.001) [Moreover, some authors described a significant correlation between MR severity and RV dysfunction. Le Tourneau et al. demonstrated that RV EF was inversely correlated to mitral effective regurgitant orifice (= 0.021) . Sabe et< 0.001) .RV structure and function have an important prognostic value in several clinical settings, especially in chronic HF, representing the marker of transition to advanced HF and worse outcome. Furthermore, most patients undergoing cardiac surgery present a variable degree of reversible or irreversible reduction in RV function, which in turn was associated with lower post-operative survival . TherefoAccordingly, an accurate assessment of RV function during pre-operative routine evaluation of MR is essential: Chrustowicz et al. analyzed a young cohort of patients with organic, severe MR by basic echocardiography and measured tricuspid annular plane systolic excursion (TAPSE), and the peak systolic velocity of the lateral tricuspid annulus (S'); a pre-operative reduction of these indices predicted a significant post-operative LV dysfunction (10% decrease in LV EF) . The samp < 0.01) in predicting 30-day postoperative mortality among patients undergoing redo valve surgery, increasing the prognostic power of EuroSCORE II at c-statistic from 0.76 to 0.83 [Finally, Mordi et al. have shown how a comprehensive preoperative echocardiography assessment of LV diastolic and RV systolic function carries an independent prognostic value  and, if possible, integrating advanced echocardiographic parameters, such as STE. Unfortunately, RV strain measurement could sometimes be challenging, due to the need of RV dedicated 4 chambers views, and poor acoustic windows with incomplete visualization of RV free wall.Overall, a preserved vs compromised RV function should represent an important element to consider in the assessment of patients’ eligibility for surgical treatment of MR.In the last years, different software implementations have been developed to assess three-dimensional strain. Area strain is a new 3D speckle tracking parameter, calculated as the percentage decrease in the size of endocardial  surface area, and determined by vectors of longitudinal and circumferential deformation at end-systole from its original area at end-diastole . It reprp = 0.004) for the prediction of cardiac events  over a mean follow up of 23.2 ± 14.5 months [Casas-Rojo et al. studied 45 asymptomatic patients with secondary MR and LVEF > 60% undergoing 3D echocardiography, showing that they had lower values of global 3D strain compared to healthy subjects and that 3D area strain greater than −41.6% reached a hazard ratio of 4.41 (5 months p = 0.018) [Interestingly, Scandura et al. used 3D strain to detect myocardial changes after MitraClip implantation. In fact, despite the absence of changes in LVEF and LV stroke volume, they showed a significant improvement in LV deformation, with the real-time 3D global longitudinal strain value changing from −9.8 ± 4.1% at baseline to −11.0 ± 4.4% at follow-up (= 0.018) .p < 0.05). Importantly, patients with pre-existing RV dysfunction showed lower increase in LV strain after clip implantation, confirming the importance of assessing RV performance also before percutaneous MR intervention. In fact, LV and RV 3D strain showed high discriminative values (AUC 0.87–0.91) in predicting lower benefits after the procedure with persistence of symptoms (NYHA > II) [Vitarelli et al.  2D and 3HA > II) .Despite these promising results, 3D strain value in clinical practice is still debatable not only due to the scarce evidence but also due to vendor-dependency and the lack of standardization. Therefore, its role in selecting patients for early surgery has not been fully established so far.The progresses in diagnostic and therapeutic management of MR have raised scientific controversies about the need of reconsidering surgical timing for these patients in order to improve their clinical outcome. The currently used criteria for referral to traditional MV operation or MV percutaneous intervention has shown some gaps in identifying patients who are developing subtle structural and functional LV and LA impairment, with sometimes consequent referral to MV repair/replacement when an irreversible myocardial damage has already occurred.The integration of STE in clinical practice, particularly using LA strain as additive criteria to indicate or discourage surgery, may represent a useful tool to improve the clinical decision-making process related to the optimal timing of intervention in patients with MR.Finally, the identification of RV dysfunction in patients with MR should be also considered an important step of pre-operative risk stratification in order to prevent a poorer outcome in the case of late surgery Fig. .


Similarly, HDFs orientation parameters improved: LVLF angle ; LVim angle . Conversely, global longitudinal strain and LVEF did not show any significant difference before and after the procedure. Echocardiographic analysis of HDFs could help differentiate patients with LV function recovery after TAVI from patients with persistent hemodynamic dysfunction.Transcatheter aortic valve implantation (TAVI) is the established first-line treatment for patient with severe aortic stenosis not suitable for surgery. Echocardiographic evaluation of hemodynamic forces (HDFs) is a growing field, holding the potential to early predict improvement in LV function. A prospective observational study was conducted. Transthoracic echocardiography was performed before and after TAVI. HDFs were analyzed along with traditional left ventricular (LV) function parameters. Twenty-five consecutive patients undergoing TAVI were enrolled: mean age 83 ± 5 years, 74.5% male, mean LV Ejection Fraction (LVEF) at baseline 57 ± 8%. Post-TAVI echocardiographic evaluation was performed 2.4 ± 1.06 days after the procedure. HDF amplitude parameters improved significantly after the procedure: LV Longitudinal Forces (LF) apex-base [mean difference (MD) 1.79%; 95% CI 1.07–2.5;  Aortic stenosis (AS) is the most common valvular disease needing intervention . TransthTreatment of severe AS is currently indicated in symptomatic patients, in those who are asymptomatic with impairment of LV systolic function without other cause, and/or for patients with very severe disease . Both suInterest in the analysis of intracardiac hemodynamic forces (HDFs) with echocardiography has grown in recent years, due to the potential to evaluate more accurately LV function and to indirectly estimate its deformation during the cardiac cycle . HDFs arThis work aims to assess HDF changes in patients undergoing TAVI for severe aortic stenosis to highlight possible adaptation of the LV to the new hemodynamic conditions after the intervention. Indeed, the acute reduction in afterload after the procedure has an effect on the contraction dynamic of the left ventricle and on the long-term positive remodeling.Consecutive patients with severe aortic stenosis referred to our center for TAVI were prospectively enrolled between March 2021 and September 2022. All patients willing to sign the written informed consent form were included in the analysis. Patients with previous surgical valve replacement and/or repair were excluded.Standard echocardiography examinations, according to current recommendations ,17, wereLV longitudinal force (LVLF) as the mean amplitude of the longitudinal force throughout the cardiac cycle; since it includes both positive and negative values, the amplitude was computed as the root mean square of all values.LV systolic longitudinal force (LVsysLF), calculated as for the LVLF above, but limited to the systolic phase only.LV impulse (LVim) as the mean longitudinal force during the systolic propulsive phase, when the force is positive (directed from the LV cavity toward the aorta); it is the area under the curve of the positive force profile during systole, normalized by the corresponding time interval .LV suction (LVs) as the mean longitudinal force during the period following propulsion while the force is negative, which is computed as the LVim but in the period comprising the end of the systole  and the initial part of the diastole .Time from R-wave to positive peak of systolic LV longitudinal force, including the rates of force generation and force decay (RtoPeak).Duration of LV negative longitudinal force in the transition from systole to diastole.Time from the start of relaxation to positive peak of diastolic LV longitudinal force.Ratio between the transverse force and the longitudinal force (TF/TL).Dominant angle of the force vector, ranging from 90°  to 0°.Reference values of normality were derived from those of healthy subjects reported in the literature . A detaiIn addition to routine echocardiographic examination, the following parameters were also collected: RV dimensions, fractional area change (FAC), RV free wall strain, RV endo strain-rate, LV inward displacement , LV endo strain-rate, LV stroke work (SW) with pressure-volume loop and hemodynamic work.t-test for continuous variables.Statistical Package for Social Sciences  was used for statistical analysis. Continuous variables were reported as mean (±standard deviation). Categorical variables were reported as percentages. We tested for normality with Kolmogorov–Smirnov test with not significant results for all variables. Comparisons between pre- and post-TAVI groups were performed by means of a paired Student’s p-value < 0.05 was considered statistically significant.Patients were then divided into subgroups, according to the presence of coronary artery disease (CAD), other cardiopathy , paravalvular leak after TAVI, gender and subtype of aortic stenosis . Analysis of variance (ANOVA) and the Mann–Whitney test were used for multigroup comparison of continuous variables. The categorical variables were compared using the chi-squared test. A 95% confidence interval (CI) was adopted and a Twenty-five patients fulfilling the study inclusion criteria undergoing TAVI were prospectively enrolled at our center. Post-procedure echocardiographic evaluation was performed 2.4 (±1.06) days after the procedure.The demographic, clinical and echocardiographic characteristics of the study population are reported in Other valvopathies were found in a significant portion of the population, with at least moderate mitral regurgitation in eight (32%) patients, at least moderate aortic regurgitation in nine (36%) patients and at least moderate tricuspid regurgitation in eight (32%) patients. Conduction disturbance was present in nine (36%) patients at baseline.p-value < 0.001)  and LVIm  were observed  and LVim angle  were significantly higher. An intergroup significant difference was also found with regards to flow rate and E/e’ avg. .< 0.001) . Statistobserved . In the After the procedure, a normalization of LVLF apex-base, LVsysLF apex-base and LVim apex-base values was observed in a greater percentage of patients, while not for the LV GLS and LVEF parameters .Finally, for the subgroups analysis, no statistically significant differences were found for the variables of interest.Our study has demonstrated that echocardiographic analysis of HDFs is feasible and can detect early adaptations to the new hemodynamic conditions after TAVI. In particular, the systolic components of hemodynamic forces (LVsysLV and LVim), as well as total hemodynamic force (LVLF), improved significantly after the procedure, highlighting how contractility recovery is related to a marked improvement in intraventricular fluid dynamics. This virtuous circle leads to an improved outward flow across the left ventricular outflow tract (LVOT), as demonstrated by significantly higher FR and lower LV filling pressure expressed by E/e’ average. Conversely, in our cohort, we observed only a marginal improvement in GLS while there was no substantial difference regarding LVEF. An increase in suction component of HDFs, albeit not significant, probably due to the presence of patients with paravalvular leak after procedure, was also observed. Not only amplitude parameters but also orientation parameters of HDFs were ameliorated after TAVI. After the procedure, the direction of LVLF and systolic components of HDFs tend to normalize as they approach 90°, with a marked reduction in transversal components .TAVI has been established as the treatment of choice in patients with severe AS at high risk for surgery . FurtherPrevious studies had already evaluated the effects of TAVI on the classical echocardiographic parameters of LV systolic function. It had been demonstrated that GLS improved after the procedure during the follow-up, and that this effect was maintained at one year ,25. HoweThis is particularly interesting in our cohort, where, of the five patients who underwent a PM implantation after TAVI, three did not present any conduction disturbances at baseline ECG, but an alteration in the profile of the HDF curve was already present before the procedure. In particular, a double systolic peak, similar to that present in patients with mild desynchrony , suggestThis study presents some limitations. This single-center, single-ethnicity study, with heterogeneous patient characteristics and a small size, does not allow the generalization of the results to the entire population. Moreover, the current approach should be considered an estimation of hemodynamic forces since the analysis is dependent on 2D image quality and frame rates. Finally, the lack of a clinical follow-up prevents the assessment of a possible association between early hemodynamic effects and long-term effects on LV function. Indeed, the majority of our patients presented with high-gradient normal-flow aortic stenosis, which is not usually associated with LVEF reduction. The results of our analysis may therefore be limited to this specific population of preserved LVEF; on the other hand, there is a strong rationale; GLS had already improved early after the procedure and suggest that changes in HDF could predict long-term remodeling.The subgroup analyses are indeed limited by the small sample size; the subgroups were chosen because they all influence cardiac hemodynamics and the LV contraction sequence. Therefore, subgroup analyses were performed as hypothesis generating, in order to observe possible relationships needing further investigation, as in the case of abnormal HDF curve and subsequent PM implantation. However, aim of the study was to evaluate the feasibility of adopting HDFs in routine clinical practice and to provide new elements for the stratification of patients undergoing TAVI.HDFs improve early after TAVI in patients with severe aortic stenosis, both in their amplitude and orientation parameters. Conversely, no significant differences were found in GLS and LVEF before and after the procedure.The clinical role for HDFs in valvular disease is still under investigation; however our findings strongly suggest a possible role for their use in the early evaluation of patients undergoing percutaneous interventions and pave the way for a new area of research.


Home mechanical ventilation is classically used to treat neuromuscular patients with chronic respiratory insufficiency. Since the heart and lungs are localized in the thorax, intrathoracic pressure may directly affect heart function. Here, we report the direct cyclic effects of mechanical ventilation on the right and left ventricular systolic and diastolic function in serial cases. These cases highlight the importance of performing Doppler echocardiography in patients with neuromuscular disorders, focusing on the right and left ventricular systolic and diastolic functions in the context of ventilation setting modifications or introduction. Neuromuscular disorders are acquired or inherited (genetic) conditions that can affect either motor neurons, the peripheral nervous system, skeletal muscles, or neuromuscular junction. Among the hereditary myopathies, Duchenne muscle dystrophy (DMD) represents the most frequent hereditary childhood myopathy, affecting approximately 19.8 in 100,000 male births worldwide . Because2O. Current transthoracic echocardiography disclosed recovered left ventricular systolic function. With mechanical ventilation, and according to insufflation, we noted modifications of the cardiac dimensions and volumes. Indeed, during the insufflation phase, we observed an increase in the LVEF, varying from 63% to 76%, a reduction in the meantime of the left ventricular end-diastolic diameter (LVEDD), from 40 mm to 32 mm, and a reduction of the end-diastolic ventricular volume (from 71 mL to 41 mL during the insufflation phase) due to the intermittent increase in the intrathoracic pressures  inhibitor because of previous left ventricular systolic dysfunction (left ventricular ejection fraction (LVEF) at 45%), and was hemodynamically stable. He was invasively ventilated because of severe respiratory insufficiency  at 8%). Mechanical ventilation was performed 24 h/24 h using the following parameters: tidal volume = 400 mL and positive end-expiratory pressure (PEEP) = 6 cmHressures .2O) because of severe respiratory insufficiency (forced predictive pulmonary VC at 6%). He took a cardioprotective drug, namely an ACE inhibitor. His past echocardiography disclosed normal left ventricular systolic function. At admission, systolic and diastolic blood pressures were respectively 110 mmHg and 59 mmHg. The electrocardiogram revealed a sinus rhythm with an incomplete right bundle branch block. Transthoracic echocardiography disclosed preserved LVEF (65%) and normal LVEDD (36 mm). We found a cyclic hemodynamic variation with a cyclic reduction of the left ventricular outflow tract flow peak velocity and a reduction of the aortic time during the insufflation phase (from 258 ms to 207 ms)  . 2O, and a respiratory rate of the ventilator at 16. She took no medications. The electrocardiogram (ECG) revealed a sinus rhythm with an incomplete left bundle-branch block. Predictive pulmonary VC was at 6%. Transthoracic echocardiography revealed a left ventricular systolic dysfunction with an LVEF at 40%, as well as a right ventricular (RV) systolic dysfunction attested by an RV annular tissue Doppler peak velocity at 8 cm/s. We found a cyclic RV systolic and diastolic dysfunction with a decrease in the RV tissue Doppler peak velocity during insufflation. The peak systolic tissue Doppler RV velocity decreased from 8 cm/s to 5 cm/s during insufflation, and the peak early diastolic tissular Doppler RV velocity decreased from 11 cm/s to 6 cm/s . She was wheelchair-bound and had a gastrostomy. Ventilation setting parameters were as follow: tidal volume 480 mL, PEEP 5 cm Ho 6 cm/s . The rato 6 cm/s . 2O) because of severe chronic respiratory insufficiency. His past medical history was pertinent for gastrostomy and thoracic drainage because of pneumothorax. Body mass index (BMI) was 36 kg/m². Systolic and diastolic blood pressures were, respectively, 118 mmHg and 70 mmHg, and the heart rate was 95 bpm. Results of the blood gas exchange were as follow: pH = 7.47, PCO2 = 29 mmHg, PO2 = 100 mmHg, and bicarbonates at 21 mmol/L. The ECG revealed a sinus rhythm with an incomplete right bundle-branch block. The echocardiography found normal LVEF (70%) and normal right ventricular systolic function. We found a cyclic diastolic tricuspid filling pattern variation with a peak early diastolic inflow tricuspid velocity (E) of 57 cm/s, decreasing to 36 cm/s during the insufflation phase, whereas the peak atrial velocity of the tricuspid inflow (A) changed from 53 cm/s to 42 cm/s during insufflation  because of severe chronic respiratory insufficiency. The patient was wheelchair-bound, and BMI was 23 kg/m². Systolic and diastolic blood pressures were, respectively, 140 mmHg and 80 mmHg, and the heart rate was 95 bpm. NT-proBNP was 54 ng/L. The ECG revealed a sinus rhythm. The echocardiography found normal systolic ventricular function (LVEF = 65%). The RV systolic function was preserved with a right fractional area change (FAC) at 55%. We found a cyclic RV systolic and diastolic dysfunction with a decrease in the RV annular tissue Doppler peak velocity during insufflation. The peak systolic tissue Doppler RV velocity decreased from 12 cm/s to 8 cm/s during insufflation, and the peak early diastolic tissular Doppler RV velocity decreased from 8 cm/s to 6 cm/s. We found, in addition, a cyclic diastolic tricuspid filling pattern with a peak early diastolic inflow tricuspid velocity (E) at 66 cm/s, decreasing to 50 cm/s during the insufflation phase, whereas the peak atrial velocity of the tricuspid inflow (A) decreased from 58 cm/s to 49 cm/s. The ratio peak early inflow tricuspid velocity/peak early tissular RV Doppler velocity (tric E/e’) was increased (tric E/e’ 8) and was stabilized during insufflation (tric E/e’ from 8 without insufflation to 8 during insufflation), illustrating the direct impact of the mechanical ventilation on venous return. A 51-year-old male patient suffering from rod congenital myopathy was admitted for cardiac evaluation in the EchoLab. He was invasively ventilated 20 h/24 h  mechanical ventilation may induce a cyclic improvement of the left systolic ventricular function associated with a cyclic reduction of the left ventricular end-diastolic volumes, an index of preload, as shown in the first case; (ii) mechanical ventilation may impede the left ventricular hemodynamics with a cyclic reduction of left ventricular outflow peak velocity, aortic time, and stroke volume, as noticed in cases 1 and 2; and (iii) finally, it may alter the right ventricle systolic function and subsequently the cyclic right ventricular systolic dysfunction. It can also affect the right ventricular diastolic filling pattern in a cyclic manner (cases 3–5).Positive-pressure ventilation increases intrathoracic pressure. Since diaphragmatic descent increases intra-abdominal pressure, the decrease in the pressure gradient for venous return is less than would otherwise occur if the only change were an increase in right atrial pressure. However, in hypovolemic states, it can induce profound decreases in venous return. Increases in intrathoracic pressure decrease left ventricular afterload and will augment left ventricular ejection. In patients with hypervolemic heart failure, this afterload-reducing effect can result in improved left ventricular ejection, increased cardiac output, and reduced myocardial O2 demand. These results illustrate the key role of the venous return and the intermittent cyclic change of hemodynamic status due to heart–lung interaction in the context of mechanical ventilation in patients with neuromuscular disorders and the tremendous emphasis of this physiological mechanism by specific patient condition. Venous return depends on the mean systemic pressure and the right atrial pressure, that is, the backpressure . The meaFor a clinical perspective and clinical practice, reducing tidal volume, reducing PEEP, and prolonging expiratory time may have a positive impact on the hemodynamic status of patients with neuromuscular disorders on mechanical ventilation . Doppler


Vertebrates developed pulmonary circulation and septated the heart into venous and arterial compartments, as the adaptation from aquatic to terrestrial life requires more oxygen and energy. The interventricular septum (IVS) accommodates the ventricular portion of the conduction system and contributes to the mechanical function of both ventricles. Conditions or diseases that affect IVS structure and function  may lead to ventricular pump failure and/or ventricular arrhythmias with grave consequences. IVS structure and function can be evaluated today using current imaging techniques. Effective therapies can be provided in most cases, although definitions of underlying etiologies may not always be easy, particularly in the elderly due to overlap between genetic and acquired causes of IVS hypertrophy, the most common being IVS abnormality. In this review, state-of-the-art information regarding IVS morphology, physiology, physiopathology, and disease is presented. Vertebrates changed the structure and function of their hearts in order to adapt to the living environment over the course of evolution. Since adaptation from aquatic to terrestrial life requires more oxygen and energy, vertebrates developed a pulmonary circulation and septated the heart into venous and arterial compartments, allowing the supply of oxygenated blood to peripheral tissues . The forIn this review, an update on adult IVS morphology, physiology, physiopathology, and disease is provided.Traditionally, gross cardiac anatomy has been described mainly based on the findings in the dissection suite. However, imaging with echocardiography, cardiac computed tomography (CCT), and cardiac magnetic resonance (CMR), have fundamentally advanced the understanding of cardiac anatomy in the 21st century . AdditioThe IVS is composed of a muscular and a membranous component. The muscular IVS component arises from the endocardial surface of the common ventricle, and has a normal thickness of approximately 9 mm in women and 10 mm in men . The comBlood supply to the IVS is predominantly derived from penetrating arteries entering from the left anterior descending artery, whereas branches from the posterior descending artery supply only the posterior third of the IVS . The IVSCardiac function is controlled by the autonomic nervous system, which consists of the parasympathetic and sympathetic divisions. In addition to the complex integration that occurs in the central nervous system, there is local intracardiac neural regulation brought about by a network of ganglionated plexuses consisting of a large number of intracardiac ganglia, and gathered in specific heart regions including the atria, the sinoatrial and atrioventricular nodes, the IVS, and both ventricles .The IVS accommodates important parts of the cardiac conduction system. The atrioventricular node is located at the apex of the Koch triangle, whereas the bundle of His divides at the juncture of the fibrous and muscular boundaries of the IVS into the left and right bundle branches . The LBB subsequently divides into anterior and posterior fascicles, which course towards the anterior and posterior papillary muscles of the LV, whereas the RBB courses down the right side of IVS near the endocardium in its upper third, deeper in the muscular portion of the IVS in the middle third, and then again near the endocardium in its lower third .Both ventricles contribute to IVS formation . CardiomDuring systole the IVS thickens and moves towards the LV after the onset of electrical depolarization followed by a brief ‘shudder’ at end systole, whereas during diastole it returns to its original thickness and position . The IVSNormal septal position and twisting are essential for ventricular function, whereas the functional interaction between the RV and LV via IVS has been termed ‘‘ventricular interdependence” ,17.Ventricular interdependence describes the influence that each ventricle has to the other as a result of the shared IVS , the encAbnormal, paradoxical septal motion (PSM), is a type of motion abnormality where the IVS movement is atypical for the particular phase of the cardiac cycle.The most common cause of PSM is left bundle branch block (LBBB) due to periods of asynchrony in contraction, ejection, end-systole, and end-diastole between RV and LV, in addition to decreased regional ejection fraction (EF) of the IVS. The LBBB usually results in two types of PSM, namely septal flash and apical rocking, which are interrelated ,24. SeptIVS ischemia/infarction is another common cause of abnormal septal motion. Experi-mental studies have demonstrated that following septal artery ligation, IVS shortening is immediately replaced by systolic lengthening ; eventuaDiastolic and systolic ventricular interactions are negatively affected in pulmonary arterial hypertension (PAH) and result in PSM. In the early stages of PAH, a rapid leftward IVS motion occurs during early LV diastole which is most likely due to prolonged RV myocardial activation . Severe A common cause of PSM is constrictive pericarditis, which is characterized by dissociation of intrathoracic from intracardiac diastolic pressures; it exaggerates diastolic ventricular interdependence due to the fixed volume in the pericardial sack resulting from the thickened, fibrotic, and/or calcified non-compliant pericardium . With inPSM may also occur after uncomplicated cardiac surgery resulting from an increase in RV transverse shortening , in order to compensate for the reduced RV longitudinal shortening , atrial HCM is characterized by increased LV wall thickness in the absence of abnormal loading conditions, such as arterial hypertension or aortic valve stenosis, that can stimulate this magnitude of IVS hypertrophy. HCM is a common inherited cardiovascular disease with a prevalence of one in 200–500 adults in the general population .HCM has been increasingly recognized as having a complex genetic etiology . Most HCHCM diagnosis is confirmed usually with echocardiography or CMR  39]. An. An39]. Basal septal hypertrophy (BSH) may be present in approximately 20–25% of patients with hypertension  or aortiVentricular septal defect (VSD) accounts for 10% of congenital heart defects in adults . VSD in Isolated septal MI is uncommon and may be due to occlusion of the septal perforator branches that supply the anterior portion of the IVS and the bundle of His. Septal involvement in MI is usually due to occlusions of the LAD or dominant right coronary or dominant left-circumflex arteries, since all of these give rise to septal branches and may lead to IVS rupture . OccasioThe IVS is important as part of the ventricular tachycardia (VT) substrate in several conditions such as idiopathic VT  as well Less common pathologies affecting the IVS include aneurysm , divertiIVS abscess development usually occurs as an extension of infective endocarditis from cardiac valves and is associated with high mortality . CardiacCardiac thrombi may occur in 2–7% in patients with atrial fibrillation or LV dysfunction, with thrombus formation occurring at the IVS in approximately 11% of the cases . IVS rupCRT is an established treatment in selected patients with heart failure . CRT in Mavacamten is a small molecule that belongs to the myosin modulators, a novel class of pharmaceutical agents that are being developed to treat patients with a range of cardio-myopathies. Myosin modulators are often classified as either “myosin activators”  or “myosin inhibitors”  . The theIn the recently completed EXPLORER-HCM , about one-third of patients on mavacamten, a myosin inhibitor that reduces myocardial contractility, achieved the primary end-point of subjective symptomatic improvement and increased functional capacity assessed by peak VO2 . This beSRT reduces LVOT obstruction in patients with HCM and includes surgical IVS myectomy and transcoronary alcohol IVS ablation. The role of surgical IVS myectomy in HCM is well established. Transcoronary alcohol IVS ablation provides a less invasive approach to septal reduction in HCM. Both surgical IVS myectomy and transcoronary alcohol IVS ablation may improve HCM patients’ functional status, with low periprocedural mortality and excellent long-term survival . As the VSD is the most common congenital heart defect. VSD creates a shunt between the RV and LV. Untreated medium or large VSDs lead to congestive heart failure . SurgicaVentricular arrhythmias originating from the LV summit and IVS account for 10–15% of ventricular arrhythmias. Managing those arrhythmias is a major challenge. Novel mapping and ablation strategies are needed in order to treat arrhythmias originating from these regions, given the current suboptimal long-term success rates with standard techniques . In thisThe IVS plays a pivotal role in cardiac function as it contributes to the structure and function of both ventricles. Conditions or diseases that affect the IVS may lead to pump failure and/or ventricular arrhythmias with grave consequences . A detai