In this article, we reviewed the development and therapeutic results of interventional devices for chordal implantation and discuss the possible clinical factors responsible for the rupture of the artificial chordal material.Mitral regurgitation (MR) was the most common heart valve disease. Surgical repair with artificial chordal replacement had become one of the standard treatments for mitral regurgitation. Expanded polytetrafluoroethylene (ePTFE) was currently the most commonly used artificial chordae material due to its unique physicochemical and biocompatible properties. Interventional artificial chordal implantation techniques had emerged as an alternative treatment option for physicians and patients in treating mitral regurgitation. Using either a transapical or a transcatheter approach with interventional devices, a chordal replacement could be performed transcatheter in the beating heart without cardiopulmonary bypass, and the acute effect on the resolution of mitral regurgitation could be monitored in real-time by transesophageal echo imaging during the procedure. Despite the  Mitral regurgitation (MR) was a common heart valve disease in clinical practice and was characterized by the backflow of blood from the left ventricle to the left atrium during diastole . A largeMitral valve repair mainly consists of annuloplasty (96.1%), leaflet resection (58.9%), and prosthetic chordae repair (29.2%) . With thArtificial chordae surgery repairs mitral prolapse or flail leaflets by replacing the diseased chords with a string-like material. This approach does not affect the surrounding valve structure and was more in keeping with the physiological anatomy of the valve. It has become the standard of care for DMR .Although surgical mitral valve repair has a good long-term therapeutic effect, it must be performed under the conditions of thoracotomy and extracorporeal circulation, which were more invasive. Compared with surgical thoracotomy, minimally invasive interventional repair devices can be performed under non-extracorporeal circulation and continous heartbeat, with the advantages of less trauma and faster postoperative recovery .The artificial chord intervention instrument was a minimally invasive interventional technique based on surgical mitral valve chordal repair, which may be divided into transapical chordal repair and transcatheter chordal repair according to the surgical approach. It could capture the prolapsed or tethered leaflet under ultrasound and/or x-ray guidance and implant the prosthetic chordae. It could also be readjusted to the appropriate length to restore leaflet alignment and reduce or eliminate MR . Many arThis review reports the development of artificial chordae materials, the principles of two routes of artificial chordae intervention devices, implantation methods, force differentials, and their clinical application effects and failure modes.in vivo, the ideal material should have the following properties: 1) High tensile strength and inelasticity to avoid fracture or deformation under the action of stress. 2) Resistance to calcification and mineral deposition to prevent hardening or fracture of the artificial chord after calcification. 3) Good fatigue properties, resistant to creep or fracture. 4) Fine, pliable, and capable of retaining this property long after implantation. 5) Porous structure that allows tissue growth to form a stable fibrous envelope and endothelial layer. 6) Good biocompatibility, resulting in producing an acceptable inflammatory response and resistance to thrombosis  sutures were the gold standard in current clinical practice for the use of artificial chordae . The ePT® ePTFE product was commercially used in clinical practice and was approved by the FDA in 1985. Two major sizes were shown in Gore’s GORE-TEXWhen ePTFE was used for artificial tendons, it was found that after a few months of implantation, the surface was covered with fibers and endothelial tissue. This discovery was a major stimulus for ePTFE research. The two pioneers who extensively tested ePTFE on animals were Frater and Revuelta . Revueltin vivo remained macroscopically smooth and pliable, with a morphology close to that of native chordae  surgical thoracotomy; 2) minimally invasive transapical implantation; and 3) transfemoral vein/atrial septal implantation . The advThe surgical method of artificial chordae implantation was to stop the heart beating with the support of extracorporeal circulation, then fully exposed the heart through a median sternotomy. The mitral valve was exposed through the right atrium-atrial septal incision or a combined right atrium-atrial septal-left atrial apex incision, and artificial chordae were implanted under direct visualization  Morris .Due to cardiac arrest, the suture length cannot be adjusted in real time to determine whether to eliminate regurgitation, and the smoothness of the ePTFE suture made tying the knot difficult, Therefore, surgeon experience was very important . The posMinimally invasive apical implantation was the implantation of ePTFE artificial chordae under 2D and 3D transesophageal echocardiographic (TEE) guidance without cardiopulmonary bypass while the heart continued to beat. In this method, only a small incision of approximately 4 cm was made in the fifth or sixth intercostal space to expose the cardiac apex of the heart, followed by deployment of the apical load and a ventriculotomy to establish the apical access  Colli e. The artTranscatheter implantation meant that the device entered through the femoral vein, punctures the interatrial septum, and then entered the left atrium and ventricle to complete the implantation of artificial chordae anchored at the edge of the valve leaflets and the papillary muscle under the guidance of echocardiography and digital subtraction techniques  Rogers . This apHowever, the success rate of transcatheter chordae implantation was low due to the length of the approach, the complexity of the mitral valve anatomy, the difficulty of the technique, and the narrow indication. It was currently in the early stages of development.Depending on the extent and location of the prolapsed area, the number and placement of the artificial chordae may vary. One study found that the artificial chordae tendineae technology could preserve the effective opening area of the valve leaflet to the maximum extent, and could effectively cope with large-scale pathological changes by inserting a plurality of artificial chordae tendineae, better preserving the systolic and diastolic function of the left ventricle . A few sSurgical implantation of artificial chordae was a technique that was gaining acceptance. This technique involved suturing one or more artificial chordae to the head of a papillary muscle and the other end of the artificial chordae to the prolapsed leaflet . The lenin vivo biomechanical study of apical versus papillary neochordal anchoring for mitral regurgitation. Force tracings were compiled for each class of chordae at baseline, after prolapse, and after both repair techniques. Baseline forces were recorded for primary (0.18 N ± 0.08 N) and secondary (0.94 N ± 0.31 N). Echocardiographic and hemodynamic data confirmed that the repairs restored physiological hemodynamics. Forces on the chordae and neochord were lower with papillary fixation than with apical fixation (p = 0.003). In addition, the maximum rate of change of force on the chordae and neochordae was higher for apical fixation than for papillary fixation . Annabel M highlighted the impact of the anchoring position of artificial neochordae and might help guide strategies to increase durability. Although the development of minimally invasive and percutaneous devices for mitral valve repair was benefiting patients by providing superior survival and freedom from reoperation, adjustments to reduce leaflet stress were essential to fully utilize these new devices.In minimally invasive apical implantation, ePTFE artificial chordae were implanted on the leaflet and the chordae were stretched until adequate leaflet coaptation was achieved and then all chordae free ends were secured to the LV wall . AnnabelChordal replacement with ePTFE strings to correct leaflet prolapse in patients with DMR was initially used for prolapse of the anterior leaflet, but over the years it was been used to correct prolapse of all segments of the MV. The use of Gore-Tex sutures as artificial chords to replace native chordal has largely been used to correct prolapse of the anterior leaflet, commissural areas, and posterior leaflet with heights of 20 mm or less. However, large, voluminous posterior leaflets with prolapse must first be treated with partial resection followed by chordal replacement. Patients with advanced myxomatous degeneration often had large posterior leaflets and associated posterior displacement of the posterior mitral annulus. In these cases, the posterior leaflet was usually trimmed to a height of 15–18 mm, and the posterior leaflet was sutured back to the endocardium of the left ventricle with running 4-0 polypropylene sutures . In DaviFinite element results  showed tIt could be said that chordal replacement with ePTFE sutures to correct mitral valve leaflet prolapse, either alone or in combination with leaflet resection all allowed a low probability of mitral valve reoperation and recurrent mitral regurgitation.n = 186 (31%)] in patients with mitral valve prolapse, generally in younger patients, and was not random but was independently associated with severe myxomatous disease with bileaflet mitral valve prolapse and marked leaflet redundancy  consecutive patients with isolated mitral valve prolapse, with comprehensive clinical, rhythmic, Doppler echocardiographic, and consistent mitral annular disjunction assessment. The presence of mitral annular disjunction was common [dundancy . Javier dundancy . All patdundancy . If neocdundancy , only trArtificial chordae interventional repair was based on the proven chordae implantation technique, which used special devices to repair the valve while the heart was beating. The following section described the principle, implantation methods, force differences, and therapeutic effects of the artificial chordae interventional devices.At present, the apical chordae repair devices that have entered the clinical stage included NeoChord DS1000 , Harpoon TSD-5 , MitralStitch , and other products. The technical difference was mainly in the method of anchoring the chordae. NeoChord and Harpoon have received CE certification .The Neochord DS1000 system was the first CE-marked transapical minimally invasive chordae repair product with over 1,700 patients implantated and was currently in FDA pivotal clinical trials. The system consisted of the Gore-Tex CV-4 size ePTFE suture. The conveyor has the following functions: valve leaf capture, optical fiber sensor detection of valve leaf capture, and artificial chordal anchor valve leaf  Rucinsk. The pron = 51). The number of chords implanted was 4.0 ± 1.1 (0–7). During the perioperative period (from procedure to discharge), the rate of mortality, stroke rate, renal failure, and atrial fibrillation rate were 0%, 0%, 0%, and 18%, respectively. Atrial fibrillation was pooled only for those without baseline atrial fibrillation (n = 50). At 1 year, 2 of the 62 patients died (3%) and 8 (13%) others required reoperation. At 1 year, 98% of patients with Harpoon cords were in New York Heart Association class I or II, and mitral regurgitation was none/trace in 52% (n = 27), mild in 23% (n = 12), moderate in 23% (n = 12), and severe in 2% (n = 1). Favorable cardiac remodeling outcomed at 1 year included decreased end-diastolic left ventricular volume (153 ± 41 to 119 ± 28 ml) and diameter (53 ± 5 to 47 ± 6 mm), and a mean transmitral gradient of 1.4 ± 0.7 mmHg. This early clinical experience with the Harpoon beating heart mitral valve repair system demonstrated encouraging early safety and performance.The Harpoon system was another transapical chordal repair device  Gammie  that difMitralStitch was the first product to offer both edge-to-edge repair and chordae repair. For edge-to-edge repair, a pair of chordae was implanted in each anterior and posterior leaflet, and the two chordae were locked together with titanium staples, resulting in a double-hole structure in the anterior and posterior leaflets  Wang et. It was In conclusion, the transcatheter apical chordae repair device was easy to operate and had a high technical success rate. Theoretically, this technique can treat not only high-risk patients who were ineligible for surgery but also young patients with low surgical risk, Which could largely replace traditional surgery and has a promising application prospect. Appropriate patient inclusion criteria were also a key factor in achieving the best results. In some complex MR anatomies, surgical repair was superior. In type A patients with isolated P2 prolapse/flail, minimally invasive implantation via the apical approach was close to the early and mid-term results of surgery. Therefore, it was an ideal entry point for transapical chordal implantation as an adjunct to surgery. However, the transcatheter approach remained the ultimate approach for artificial chordae, as the apical approach was still traumatic and carried the risk of long-term pericardial adhesion.Transcatheter chordae repair devices had attracted much attention due to their lower trauma and better compliance with the physiological and anatomical structure. However, due to their technical difficulties, the products were currently in animal experiments or early clinical stages, including NeoChord NeXuS , CardioMech   Rogers , and Pipin vivo experiments in sheep, and both showed good healing of at 90 days. Animal experiments with the Pipeline system also confirmed that the metal anchors did not damage the papillary muscle. These experiments provided preliminary confirmation of the in vivo safety of metal anchors for anchoring the papillary muscle.Unlike transapical artificial chordae devices, transcatheter devices required the implantation of metal anchors to hold sutures to the papillary muscle, which may carry the risk of damaging the papillary muscle. Animal studies of the Neochord NeXuS system reported at the Transcatheter Cardiovascular Therapeutics (TCT) conference showed that the anchor nail on the papillary muscle was covered by fibrous tissue and endothelium at 90 days. Overall, the papillary muscle healed well overall and no obvious necrosis was observed. Transcatheter chordae repair devices were still in the early stages of development due to their technical difficulty, and only a few clinical trials were reported. Unlike other solutions, the CardioMech system  protocolThe Neochord NeXuS system was a product based on the DS1000 for transfemoral/interatrial septal access that accessed the left atrium through a large 28F sheath via the femoral vein, captured the leaflet under the guidance of TEE and confirmed by a fiber optic sensor, and finally achieved multiple chords attached to a papillary muscle metal screw anchor. Currently, Transcatheter chordae repair devices might be a viable and feasible option for the treatment of isolated single-leaflet prolapse in the future, with a good risk-benefit ratio. However, the technique and procedures were more complex with many steps and were still in the early stages of development, requiring stable devices, long-term follow-up, and more cases to confirm these preliminary results.Transapical implantation of ePTFE chordae under beating heart condition was a minimally invasive interventional therapy with a very low rupture rate and proven durability and long-term results in a 25-year study published in 2013 , showingThe long-term durability of transapical artificial chordae implantation was still unknown, so it was very important to understand the potential mechanism of chordal rupture.The durability and long-term effects of artificial chordae were closely related to the amount of force applied to them, and excessive force could lead to chordae rupture. The anchoring position and the length of the artificial chordae influenced their force. Surgical thoracotomy and transcatheter artificial chordae tended to be anchored to the leaflet and papillary muscles, whereas transapical chordae implantations tended to be leaflet and the apex. Since artificial chordae implantation led to post-reconstruction shrinkage of the left ventricle, the length of the artificial chordae was often shortened somewhat from the optimal length to avoid recurrent MR . For apiDifferences in chordae implantation techniques might have a significant impact on the durability of the ePTFE artificial chordae. We found several cases of chordae rupture in the “loop” implantation technique  Duran a, probablCalcification might be one of the causes of the late rupture of ePTFE artificial chordae. The rupture of the ePTFE artificial chordae might also be related to the suture specification. First, in all of the above cases, the sutures that ruptured were mainly CV-5 ePTFE sutures. Mutsuga reviewed the failure cases of using ePTFE artificial chordae from 2002 to 2020. One (0.5%) of 186 patients using CV-4 ruptured at 78 months. In addition, 6 (3.9%) of 154 patients using CV-5 ruptured at 44–201 months. The durability of CV-4 specification ePTFE suture might be better than CV-5  Mutsuga. TherefoThere were also some cases where fracture factors were not described. Nakaoka reported a patient with three pairs of CV-5 ePTFE implanted in the anterior leaflet, in which one pair of ePTFE ruptured after 7 years, and the suture was thickened . Yeo desAt present, the use of ePTFE artificial chordae to resolve mitral valve prolapse caused by extended or ruptured native chordae has become a mature method with a clinical history of more than 35 years, providing stable valve function and clinical outcomes in most patients with DMR. The long-term durability of ePTFE played a key role, which was closely related to its physicochemical properties and biocompatibility. Although this technology was safe and effective, there were still cases of ePTFE artificial suture rupture occurring due to chordae calcification, friction, surgical injury, and excessive force. Therefore, when performed artificial chordae repair, some measures could be taken to reduce the probability of this adverse event, such as 1) paying attention to chordae implantation and suturing techniques to avoid frictional damage to the sutures; 2) increasing the number of chords to reduce the force distributed on each suture; and 3) using CV-4 instead of CV-5, which had a thicker string diameter and stronger mechanical properties.Artificial chordae interventional devices had gradually become a substitute therapy for high-risk DMR patients, providing physicians with a variety of options. The two different types of devices had their own advantages and disadvantages. Among them, the transapical chordae repair devices had more clinical data, relatively simple technique and operation, and a high success rate, but it was traumatic, and the force on the chordae was greater than the papillary muscle anchoring. Transcatheter chordae repair devices were in the early investigational phase with limited clinical data. Their advantages include less trauma and anchoring of the chordae to the papillary muscle, which was closer to the physiologic and anatomic structure. However, they had narrow indications and anatomical limitations, and the technique and operation were relatively complex. In the future, clinical studies with larger sample size and longer follow-up are necessary to confirm the long-term outcomes and patient selection criteria.(1) More physiological.(2) Less impact on mitral valve hemodynamics.(3) No interference with future secondary surgical procedures.(4) Feasibility for low-risk, low-grade patients.As an important part of the interventional mitral valve treatment technology, transcatheter chordae repair technology will continue to be a mainstream development direction in the field of interventional mitral valve treatment in the future, which has unparalleled advantages over interventional mitral valve replacement such as:The continued emergence of interventional transcatheter chordae repair devices via the femoral vein also meant that a solid step had been taken in this technical field and that it still had a wild prospective.For the patients with prolapse but no significant dilatation of the valve ring, whose cardiac function was still good, interventional transcatheter chordae repair devices were the most beneficial for them at that time.However, in high-risk patients with severe mitral regurgitation leading to the stage of heart failure, the lack of clinical experience with simple interventional artificial chordae repair and the existence of distant recurrent regurgitation risk, which to some extent limits the application of artificial chordae, but we still have reason to believe that with the accumulation of experience and the progress of technology, the complete intervention of mitral valve repair will no longer be an unattainable dream.


Evaluation of diastolic function parameters revealed statically significant differences between the patients and controls regarding Edt , E/E’ , and IVRT . Left atrial function was impaired in the study group compared to controls: LAVI , AC-CT , and AC-R-, respectively. VO2 max in the study group reached 33.1 ± 6.2 ml/min/kg. A statistically significant, moderate, negative correlation between VO2 max and E/E’  was found. Left ventricular diastolic function is impaired and deteriorates with the arrhythmia burden increase in PVC children. Ventricular arrhythmia in young individuals may be related to the filling pressure elevation and drive to exercise capacity deterioration.Premature ventricular contractions (PVC) are frequently seen in children. We evaluated left ventricular diastolic function in PVC children with normal left ventricular systolic function to detect whether diastolic function disturbances affect physical performance. The study group consisted of 36 PVC children, and the control group comprised 33 healthy volunteers. Echocardiographic diastolic function parameters such as left atrial volume index (LAVI), left atrial strains , E wave, E deceleration time (Edt), E/E’ ratio, and isovolumic relaxation time (IVRT) were measured. In the cardiopulmonary exercise test (CPET), oxygen uptake (VO Risk factors, such as frequent PVCs, short coupling intervals between the sinus and premature beat, retrograde P-waves, broad QRS complexes, and complex arrhythmia, may induce systolic dysfunction6.Premature ventricular contractions (PVCs) are among the most common rhythm disorders. They are frequently observed in children and adolescents without structural heart disease and are considered benign. However, this hypothesis is uncertain due to existing observations indicating some connections between PVCs and left ventricular systolic dysfunction8. This issue has not been investigated in children yet. In the recent data from our center, it was detected that exercise capacity is lowered in young individuals with PVC even if the left ventricular systolic function is normal9. This finding raises the question: what is the reason for these circumstances? One of the hypotheses is that the reason for low exercise capacity is dyssynchronous contraction. Nevertheless, we know that left ventricular diastolic dysfunction relates to the decrease of exertion tolerance in some clinical scenarios13.Moreover, there are data in the literature showing that in adults with PVC and normal ejection fraction, some diastolic function parameters, such as left atrial volume or diastolic filling pressure of the left ventricle, are impairedConsidering these data, we aimed to evaluate the left ventricular diastolic function in young individuals with frequent ventricular arrhythmia and normal left ventricular systolic function, to detect whether potential diastolic function disturbances influence physical performance.The study for prospective research was approved by the Bioethical Committee of the Medical University of Warsaw, No. 98/2020 dated June 15, 2020. The research reported in this paper adhered to all relevant guidelines and regulations including the Declaration of Helsinki. All the participants and their legal guardians signed an informed consent form before involvement in the study.The present study was conducted prospectively between January 2022 and June 2022. The study group consisted of 36 patients of both sexes , aged 12 to 17 years, in whom extra beats were detected by auscultation or ventricular arrhythmia was registered in ECG evaluation during well-child visits. The primary inclusion criteria were as follows: age range 8–18 years, newly diagnosed, meaning not more than 3 months before the study, frequent ventricular arrhythmia, defined as at least 10% premature ventricular contractions on Holter ECG monitoring, and feasibility to perform cardiopulmonary exercise testing (CPET). Children with pharmacologically treated arrhythmia were excluded from the study group. Thirty-three age- and sex-matched healthy volunteers  were enrolled during the same study period as a control group. The overall hours of activity per week were registered during the history taking. Exclusion criteria for both groups were age below 8 years or 18 years and above, any coexisting cardiac disorders or chronic comorbidities not allowing proper CPET performance, and more than 4 h organized physical activity per week. In the physical assessment, the following anthropometrical measurements and vital signs were performed: weight, height, body surface area, body mass index (expressed as z-score), heart rate, and blood pressure.All patients and controls underwent resting ECG, 24-h Holter monitoring, echocardiography, and CPET.Twelve-lead electrocardiograms were recorded using BioCare ECG . The heart rate, PR, QRS, and QT intervals were measured. QTc was calculated according to the Bazzett formula. The morphology of ventricular extra beats, including the QRS duration, bundle branch block pattern, and the axis of the QRS in limb leads, were assessed. Moreover, 24-h Holter recordings were made using Pathfinder SL , in which minimal, maximal, and mean heart rates were registered in the study and control group. Additionally, arrhythmia number and burden were registered in the patients. Frequent arrhythmia was defined as a 10% burden in the 24-h Holter ECG. One cardiologist analyzed the recordings, unaware of the subjects’ other data.Conventional transthoracic echocardiography was performed using an EPIQ CVx 5.0 ultrasound machine . Two-dimensional guided M-mode, pulsed wave Doppler, tissue Doppler (TDI), and speckle tracking echocardiograms were performed in parasternal short-axis and apical views. The frequencies of the sector array used in the study ranged from 2.1 to 4.2 MHz.14. Left ventricular ejection fraction (LVEF), representing LV systolic function, was determined using the Simpson method from 4-chamber and 2-chamber apical view imaging. Left ventricular shortness fraction  was calculated in M-mode imaging. The normal systolic function was defined as a LVDd within the normal limit and EF 55% or more.LV end-diastolic dimension  and end-systolic dimension , interventricular septal diastolic diameter , interventricular septal systolic diameter , left ventricular posterior wall diastolic diameter , and left ventricular posterior wall systolic diameter  were measured at the level of the top of the papillary muscles in M-mode imaging. These parameters were indexed to the body surface area and expressed as the z-score Mitral inflow velocities were obtained from pulsed-wave Doppler in the apical 4-chamber view. Early diastolic mitral inflow velocity , atrial diastolic mitral inflow velocity , and E deceleration time  of the E wave were measured as diastolic echocardiographic variables. Isovolumic relaxation time , early diastolic , and late diastolic  velocities were measured at the septal mitral annulus using the tissue doppler imaging method (TDI). The ratio between E and E’ (E/E’) was calculated as an indicator of LV filling pressure.15. It was indexed to body surface area . LA function measures were performed using speckle tracking echocardiography in apical 4-chamber view with the R–R gating. Three variables were assessed. Firstly, the reservoir strain , the first peak between the R wave and the T wave during left ventricular systole, reflects the left atrial filling. Secondly, the conduit strain  reflects the left atrium emptying during the early diastole of the left ventricle. Thirdly, the contractile strain , starting on the P wave, reflects the booster pump function of the left atrium. For each parameter, 3 consecutive cardiac cycles were averaged, avoiding PVCs. Analysis of echocardiographic data was performed by an investigator who was unaware of the other data in the study and control group.Left atrial volume was evaluated using the biplane area-length method from 2 orthogonal apical views, as recommended by the American Society of Echocardiography2), and carbon dioxide production (VCO2), were continuously monitored. The respiratory exchange ratio (RER) (VCO2/VO2) was simultaneously calculated and used to assess maximal effort. The trial ended when the patient could not maintain the pedal cycle rhythm. No study was interrupted due to cardiopulmonary complications. CPETs were considered valid if the VO2 reached a plateau (> 1 min) despite increasing workload and/or a complementary respiratory exchange ratio (RER) was ≥ 1.05 combined with peak heart rate above 85% of predicted. Maximal oxygen uptake (VO2 max) was defined as the oxygen uptake during maximal exercise and was indexed to body weight and time and expressed in milliliters per kilo per minute.All patients and controls performed symptom-limited, upright-sitting cardiopulmonary exercise test (CPET) with an incremental RAMP protocol on a bicycle ergometer. After a 3-min rest period, unloaded paddling was made at a rate of 60 rpm for 2 min. The effort was then progressively increased by 10–15 watts/min until the patient could no longer continue a cycling frequency of at least 40 rpm. Cardiopulmonary parameters, such as heart rate, oxygen uptake . Variables were presented as mean ± standard deviation or median , depending on data distribution. Distribution normality was assessed using the Shapiro–Wilk test and based on skewness and kurtosis values and visual assessment of histograms. The study and control group were compared with an independent t-test or Mann–Whitney U test, depending on the data distribution. The data were presented as the mean/median difference (MD), including a 95% confidence interval (CI). Additionally, the correlation between continuous variables was verified with Spearman correlation coefficients. To classify the reliability of correlations we used the scale presented in the supplementary file. Table S1p = 0.82. There were no obese children in the study and control group; overweight was seen in one patient of the study group but in none of the control group. The anthropometrical data and vital signs in the study group and controls are presented in Table All the patients were newly diagnosed with arrhythmia. The mean age in the study group was 13.8 ± 2 years, and in controls it was 13.2 ± 3 years. None of the children in the study and control group had chronic comorbidities. None of them had clinical signs suggesting arrhythmia presence, and they were not pharmacologically treated when all the tests during the study were performed. Patients and controls had a similar level of everyday organized physical activity of up to 4 h per week at school. Overall physical activity per week was 4.9 ± 1.4 h in the study group and 5.1 ± 1.1 h in the control group, In the study group, the median number of PVCs for 24 h was 19,976 beats , accounting for 20.5 ± 12.1% of the arrhythmia burden. In 28 (78%) patients inferior axis, and in 30 (83%) patients left bundle branch block morphology of PVC was registered. In 8 (22%) and in 6 (17%) patients superior axis and right bundle branch morphology of PVC were seen, respectively. The mean VES QRS duration of PVC was 170 ± 21 ms. In all children of the control group normal sinus rhythm in the ECG and 24-h Holter monitoring was registered, and none of them had ventricular arrhythmia. All the basic parameters during the sinus rhythm in the rest ECG and 24-h Holter ECG are summarized in the supplementary file. Table Left ventricular performance and systolic function.p > 0.5, including LVDd , LVDdi , EF , and SF . All the data on left ventricular performance and systolic function parameters are summarized in Table All the systolic parameters in the study and control group were assessed as normal, and after comparison between the study and control group they were not statistically significant, p < 0.01). Evaluation of tissue Doppler imaging (TDI) parameters showed significant (p < 0.01) differences between the study group and controls regarding IVRT  and E/E’ ratio . The differences between the study and control groups regarding left atrial parameters such as LAVI , AC-CT , and AC-R  were also statistically significant (p < 0.01). The assessment of the study group regarding the number of patients with various disturbed diastolic function parameters is summarized in Table 18.A comparison of the study group vs. controls regarding diastolic and left atrial parameters is summarized in Table During CPET, patients and controls achieved maximal effort, with RER ≥ 1.05 and a peak heart rate of 85% of the predicted value. In the study group, the resting heart rate was 94 ± 17 bpm, and the maximal heart rate was 186 ± 11 bpm. The maximal oxygen uptake (VO2 max) in the study group reached 33.1 ± 6.2 ml/min/kg in controls. The exact data on CPET parameters in the study and control groups are summarized in Table p < 0.01). Figure A moderate, statistically significant, positive correlation was detected between the IVRT and arrhythmia burden . Figure Furthermore, a moderate, negative correlation between maximal oxygen consumption VO2 max) and E/E’ ratio was detected  are usually benign. Rarely, they may lead to the contractile dysfunction called “arrhythmic cardiomyopathy”.8, where the indexed left atrial volume correlated statistically significantly with the arrhythmia burden. In our pediatric population, contrary to the study by Park et al., the correlation between arrhythmia burden and left atrial parameters was weak and not statistically significant. There are several explanations for this discrepancy. Firstly, in the cited data, the degree of linear correlation between PVC burden and left atrial size could have been stronger despite a larger study population (146 patients) than ours (36 patients). Secondly, the cited trial was performed in a relatively old population (mean age 55 years) compared to ours (mean age 14 years), so left atrial size, reflecting left ventricular filling pressure, may relate not only to PVC burden but also to the low compliance of the myocardium due to its degeneration, which could to some extent empower increased filling pressure associated with the ventricular arrhythmia.Among these parameters, the most obvious in children with ventricular arrhythmia was left atrial enlargement and its functional disturbances expressed as strain parameters (reservoir and contractile strain). The left atrial enlargement was already described in adults with PVC in the study of Park et alFurthermore, we found statistically significant differences between the controls and patients regarding left atrial strain variables. The cut-off limits of left atrial strains for children are not established, so the meaning of our findings is uncertain. Further detailed evaluation on a bigger cohort would detect cut-off limits of left atrial strains for PVC children and shed light on the clinical value of these findings.20.The elongation of the E deceleration time (Edt) in our study group suggests that ventricular diastolic dysfunction is at the disease’s initial stage. In general, Edt preservation is closely connected with diastolic function impairment severity. In adults, the elongation of Edt is often seen as a physiological process due to the gradual decline of the myocardial compliance with age, but in young humans it reflects early diastolic left ventricular stiffness due to mildly impaired relaxation. Pseudo-normal or mildly reduced Edt is a sign of concomitant concentric left ventricular hypertrophy, and markedly reduced Edt means restrictive filling and advanced diastolic dysfunctionIn our patients, the elongation of Edt was probably observed as a reflection of mild relaxation disturbances. We can only speculate that in some patients, during long-term follow-up, the diastolic function would deteriorate further, leading to the irreversible stiffness of the ventricle if proper antiarrhythmic treatment was not performed.22 In PVC children, it is the consequence of dyssynchronous contraction due to arrhythmia, which leads in a natural way to dyssynchronous relaxation. The dyssynchronous myocardial activation is seen not only when a premature beat occurs but also during sinus rhythm neighboring the premature contraction23. It probably normalizes gradually from beat neighboring to beat remote from PVC. The evidence for the last assumption does not exist in the literature and needs some further investigation. Still, it could explain why IVRT relates to the arrhythmia burden in our patients.To some point, isovolumetric relaxation time (IVRT) analysis confirms our hypothesis. IVRT was also found to be elongated in our population, which, to the best of our knowledge, was never described in the literature concerning PVC in children. Its increase relates to early diastolic dysfunction in many diseases such as hypertrophic cardiomyopathy, arterial hypertension, or diabetes20. Our results are concordant with the study of Salem et al.7 in which it was significantly higher in adults with PVC than in the controls. Moreover, our recent trial found a statistically significant correlation between exercise capacity and E/E’. The elevated filling pressure of the left ventricle is strictly related to the low exercise capacity in many diseases, e.g., aortic stenosis, atrial fibrillation, or diabetes13. Considering such data, we may assume that high E/E’ in children with PVC may reflect increased filling pressure, which probably does not normalize during effort and directly influences exercise capacity. Another possible explanation is that dyssynchronous contraction is the primary factor connected with the low exercise capacity, and the diastolic filling pressure is less meaningful for the exertion tolerance in PVC patients. We can assume that further analysis using detailed hemodynamic evaluation, e.g., stress echocardiography, would help explain the mechanism of low exercise capacity in young individuals with ventricular heart rhythm disturbances.Another diastolic function parameter disturbed in adolescents with PVCs is the E/E’ ratio. It was significantly higher in the cases than in the controls. E/E’ is the primary factor reflecting the filling pressure of the left ventricle, which, according to the guidelines, has become one of the essential noninvasive diastolic function parametersIn conclusion, left ventricular diastolic function is impaired and deteriorates with the arrhythmia burden increase in PVC children. Ventricular arrhythmia in young individuals may be related to exercise capacity decrease due to the left ventricular filling pressure elevation.In our study, we did not precisely perform the modified Borg RPE score and did not use it as an inclusion criterion. In our opinion, self-assessment of the exertion level is frequently inadequate in the pediatric population. However, our department has a routine clinical practice to evaluate the level of perceived exertion during the CPET. The test is valid only if the modified Borg RPE score is 7/10. All the patients in the study group and the controls had valid tests, which means that all of them achieved at least grade 7 on the modified Borg RPE scale.We did not evaluate an exact number of hours of activity. Nonetheless, all the patients and controls had a similar level of everyday physical training of up to 4 h of recreational sport per week at school. We also did not record the exact results of laboratory tests such as the blood cell count and ion balance. Basic laboratory tests were performed in all patients due to clinical evaluation, and all the results were normal or insignificant from the clinical point of view.This is a pilot study. A detailed analysis of the diastolic function in a larger cohort of patients with ventricular arrhythmia is necessary to confirm our findings. Moreover, the significant correlations between chosen parameters were only moderate in our patients. Thus, it needs to be confirmed in the future whether any link between diastolic dysfunction and physical performance and arrhythmia burden in PVC children exists.Supplementary Information.


In recent years, there has been growing interest in exploring the relationship between activities of daily living (ADL) and cardiovascular diseases. This retrospective cross-sectional study aimed to investigate the association of ADL measured by Barthel index (BI) with periprocedural myocardial infarction (PMI) and injury following percutaneous coronary intervention (PCI).Enrolled patients were stratified into impaired and unimpaired ADL groups according to their BI scores. Logistic regressions were conducted to explore the association of ADL on admission with periprocedural myocardial injury and infarction. Restricted cubic spline (RCS) curve and subgroup analysis were also performed.P = 0.011) and injury . Subgroup analysis showed that the association between ADL and PMI was founded in several subgroups, while the association between ADL and periprocedural myocardial injury was founded only in BMI ≥ 24 kg/m2 subgroup.Totally, 16.4% of patients suffered from PMI; the mean age was 65.8 ± 10.4 years old. RCS analysis showed that the morbidity of periprocedural myocardial infarction and injury showed a downward tendency with increasing BI scores. Multivariable logistic regression analysis demonstrated that impaired ADL was an independent risk factor for periprocedural myocardial infarction (OR = 1.190, 95% CI , Impaired ADL at hospital admission was an independent risk factor for periprocedural myocardial infarction and injury among patients following PCI.The online version contains supplementary material available at 10.1186/s12872-023-03468-5. Coronary artery disease (CAD) is a leading cause of mortality worldwide , 2. CurrAs the global population continues to age, there has been a growing focus on individual capacity to perform everyday tasks, known as activities of daily living (ADL), in clinical settings. The Barthel index (BI), a highly reliable and valid tool, is commonly employed to assess a patient’s ability to perform necessary ADLs during the rehabilitation process , 18. A 2Thus, this retrospective study was conducted to assess whether ADL at admission could predict periprocedural myocardial infarction and injury, and to offer suitable preventive and management strategies for patients undergoing PCI.This study was a retrospective review of all consecutive eligible patients following PCI from March 2005 to August 2021 at Sir Run Run Shaw Hospital and its medical consortium hospitals. Additional details about the study subjects are listed in Fig. Various parameters involving patient demographics, clinical features, laboratory results, medications, and angiographic characteristics were extracted from the hospital information system.Healthcare professionals routinely evaluate BI score upon hospital admission. The BI score was recommended as an assessment of ADL. The BI score consists of 10 items about feeding , grooming , bathing , dressing , bladder control , toilet use , bowel control , ambulating , chair transferring , and stair climbing  . The oveBased on the latest revised fourth universal definition of myocardial infarction (UDMI) published in 2018, periprocedural myocardial infarction was defined in this study as an increase in cTnI levels greater than 5 times of the upper reference limit (URL) within 48 h following PCI, in addition to one or more of the following: (1) the clinical criteria, manifested with prolonged chest pain attributed to ischemic changes (≥ 20 min); (2) ECG criteria, including ischemic ST changes or new pathological Q waves; or (3) imaging criteria, manifested with imaging evidence of new loss of viable myocardium or new regional wall motion abnormality or angiographic evidence of a flow-limiting complication . PeriproStatistical analyses were performed using SPSS software version 22.0  and R version 4.0.5 . Continuous variables were expressed as mean ± standard deviation (SD) and compared using T-test in case of normal distribution, while expressed as median (interquartile range [IQR]) and compared using Mann-Whitney U-test in case of non-normal distribution. Categorical variables were expressed as counts (percentage) and compared using Chi-Square test or Fisher’s exact test.2), NT-proBNP (×103pg/mL); Model 3 based on Model 2, additionally adjusted for CTO (yes or no), calcification (yes or no), rotational atherectomy (yes or no), LMPCI (yes or no), multivessel PCI (yes or no) and total stent length (mm). Restricted cubic spline (RCS) curve according to Model 3 correction was performed for visualization analysis. Based on age (≥ 65 or < 65 years old), ever smoked (yes or no), BMI (≥ 24 or < 24 kg/m2) and eGFR (≥ 60 or < 60 ml/min/1.73m2), subgroup analysis was performed to test whether the association of the ADL with the occurrence of periprocedural myocardial injury and infarction was constant.Univariant and multivariate logistic regression were used to determine the association of the ADL at hospital admission with periprocedural myocardial infarction and injury. The previously recognized risk factors variables of periprocedural myocardial infarction and injury from previous studies were included as covariates in the multivariate regression analysis , detaile11,028 patients were enrolled, and the mean age was 65.8 ± 10.4 years old. Patients with impaired ADL accounted for 17.6%. The incidence of periprocedural myocardial injury was 46.6% , and periprocedural myocardial infarction was 16.4% .P < 0.001); higher cTnI fold-elevation, higher levels of baseline white blood cell (WBC), C-reactive protein (CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and lower levels of estimated glomerular filtration rate (eGFR) and platelet counts  also were noted among this group of patients in comparison with patients without occurring periprocedural myocardial infarction. In terms of vessel conditions and procedure data, periprocedural myocardial infarction patients had higher proportions of calcification , CTO , rotational atherectomy , LM PCI , multivessel PCI , and longer total stent length . The medication characteristics of periprocedural myocardial infarction patients were reflected in a higher proportion of use of angiotensin converting enzyme inhibitor/angiotensin receptor antagonist (ACEI/ARB), beta-blockers, calcium channel blockers (CCB) .Table P < 0.001).The significance of the intergroup differences in the above variables could be observed almost immediately when grouping by whether periprocedural myocardial injury had occurred or not Table . PatientAs shown in Fig. P < 0.001). After adjusting for age, renal dysfunction, and NT-proBNP (shown in Model 2), and further adjusting for vessel conditions and procedure data  (shown in Model 3), multivariable linear regression analysis demonstrated that impaired ADL was an independent risk factor for the incidence of periprocedural myocardial infarction .The study used univariable and multivariable logistic regression analysis to investigate the association between ADL and periprocedural myocardial infarction incidence Table . Model 1P = 0.034), renal dysfunction , elevated NT-proBNP , CTO , calcification , rotational atherectomy , LM PCI , multivessel PCI  and increased total stent length  were independent risk factors for the incidence of periprocedural myocardial infarction .As described in Table 2), and eGFR (≥ 60 or < 60 ml/min/1.73 m2). Impaired ADL was significantly associated with the increasing incidence of periprocedural myocardial infarction in age ≥ 65 years old , ever smoked , BMI ≥ 24 kg/m2  and eGFR ≥ 60ml/min/1.73m2  subgroups. The association between impaired ADL and periprocedural myocardial injury was significant only in BMI ≥ 24 kg/m2  subgroup.Figure In this retrospective cross-sectional study, the morbidity of periprocedural myocardial infarction and injury was approximately 16.4% and 46.6%, respectively. The results revealed a negative correlation between BI scores and the incidence of periprocedural myocardial infarction and injury. Impaired ADL at hospital admission emerged as an independent risk factor for periprocedural myocardial injury and infarction. Exploratory analysis indicated that the association of impaired ADL with periprocedural myocardial infarction was more robust than with periprocedural myocardial injury. The current research emphasized the importance of assessing ADL scores at hospital admission for patients intending to undergo PCI. Physicians should be aware of the increased possibility of periprocedural myocardial infarction and injury events in patients with impaired ADL at hospital admission.Periprocedural myocardial infarction and injury remain frequent life-threatening complications in cardiac revascularization, especially in PCI, as these complications are associated with the PCI procedure in cath lab settings . PeriproADL indicates individual self-care ability, encompassing activities such as self-feeding, toileting, and mobility. It does not function only as a tool for assessing the body’s condition, but also it serves as an indicator of overall health. There are several standard scales that are employed to estimate a patient’s ADL, including the Stanford Health Assessment Questionnaire Disability, the Katz index, and the BI –32. The Impaired ADL often coexists with aging, inflammation, and organ dysfunction, including cardiac and renal dysfunction, which are well-established risk factors for periprocedural myocardial infarction . A recenThe relationship between ADL and periprocedural myocardial infarction and injury is multifactorial; however, the underlying mechanisms have yet to be fully elucidated . A recenThis study had several limitations that warrant further discussion. Firstly, like any retrospective research, it had inherent biases that could not be entirely avoided, such as confounding bias, selection bias, and information bias. Therefore, large-scale prospective studies need to be conducted to validate the findings. Secondly, the population distribution of the BI scores in this study was highly skewed, making it much more challenging to classify ADL into traditional categories of normal function (BI = 100), mild dysfunction (60–99), moderate dysfunction (40–59), severe dysfunction (20–39), and very severe dysfunction (BI < 20). This was attributed to the fact that the participants included in this study were all scheduled for elective PCI procedures, which compared to patients undergoing emergency PCI, generally had better self-care abilities. Consequently, the majority of patients exhibited normal ADL. Additionally, in the prevalent cultural practices of China and even Asia, individuals tend to conceal their symptoms of suffering , which mImpaired ADL at hospital admission was an independent risk factor for the incidence of periprocedural myocardial infarction and injury among patients following PCI. Along with the reduction in BI scores, there is a noted upward trend in the incidence of periprocedural myocardial infarction and injury. The results were significant for preventing and treating periprocedural myocardial infarction and injury in the clinic. Clinicians may consider integrating ADL assessment into the routine pre-procedural evaluation to effectively stratify patients and customize their management plans accordingly. Tailored monitoring protocols should be formulated for these high-risk patients before and after the procedure, including more frequent cardiac biomarker measurements and electrocardiographic monitoring, to ensure early detection and timely intervention.Below is the link to the electronic supplementary material.Additional File 1: Baseline characteristics grouped by periprocedural myocardial injury or not.


Late gadolinium enhancement (LGE) is a valuable part of cardiac magnetic resonance imaging (CMR). In particular, inversion-recovery imaging of LGE, with nulling of the signal from reference areas of myocardium, can have a distinctive pattern in some patients with cardiac amyloid, including both diffuse (relatively faint) subendocardial LGE and a relatively dark appearance of the blood. However, the underlying reasons for this distinctive appearance have not previously been well investigated. Pharmacokinetic modeling of myocardial contrast enhancement kinetics can potentially provide insight into the mechanisms of the distinctive LGE appearance that can be seen in cardiac amyloid, as well as why it may be unreliable in some patients.An interactive three-compartment pharmacokinetic model of the dynamics of myocardial contrast enhancement in CMR was implemented, and used to simulate LGE dynamics in normal, scar, and cardiac amyloid myocardium; the results were compared with previously published values.The three-compartment model is able to capture the qualitative features of LGE, in patients with cardiac amyloid. In particular, the characteristic “dark blood” appearance of PSIR images of LGE in cardiac amyloid is seen to likely primarily reflect expansion of the extravascular extracellular space (EES) by amyloid in the “reference” myocardium; the cardiac amyloid contrast enhancement dynamics also reflect expansion of the body EES.The distinctive appearance of LGE in cardiac amyloid is likely due to a combination of diffuse expansion by amyloid of the EES of the reference myocardium and of the body EES.The online version contains supplementary material available at 10.1186/s12968-023-00952-x. Cardiac involvement in amyloid deposition can lead to heart failure; it can sometimes be difficult to diagnose without biopsy. Cardiac magnetic resonance imaging (CMR) has been reported to be useful in the diagnosis of cardiac amyloid. In particular, as reported by Maceira et al. , there cIt is likely that the more rapid clearance of the contrast agent from the blood pool in cardiac amyloid found in  reflectsWe have informally observed that there are also some cases where a “characteristic” appearance of cardiac amyloid seen on LGE images in some patients was not confirmed by subsequent myocardial biopsy; on the other hand, there are some other cases where amyloid was incidentally found on a biopsy of the myocardium, but prior LGE images did not show the characteristic appearance of cardiac amyloid . The poThe purposes of this study were to: (1) create an interactive computer program to qualitatively and quantitatively model the dynamics of LGE in the heart, 2) use this program to assess the likely relative contributions of different physiologic factors (particularly amyloid-induced expansion of the EES in the body and in the myocardium) in producing the characteristic LGE appearance of cardiac amyloid, and then 3) use the program to assess some likely reasons why the LGE appearance in CMR and the corresponding presence or absence of cardiac amyloid on biopsy may be discrepant in some patients. This modeling process is challenging, due to the lack of direct knowledge of many of the underlying parameter values and the relatively limited observational data available for estimating them. However, suitable modeling of the LGE dynamics can help to constrain the number of relevant physiologic parameters that need to be considered and their range of likely values [ use this use the As mentioned above,  also meaAs the characteristic reported changes in cardiac amyloid contrast enhancement are evident by imaging relatively late (minutes) into the enhancement process, we will not attempt to model the more complex effects of the initial redistribution of the contrast agent bolus within the circulating blood (including recirculation), nor the initial “first-pass” myocardial enhancement dynamics (reflecting perfusion). We will assume that the contrast agent distribution is confined to the extracellular space (blood plasma and tissue interstitium). After the initial (relatively transient) events of the distribution of contrast agent around the circulating blood after a bolus injection, the kinetics of the average plasma contrast agent concentration will be predominantly determined by two processes: 1) exchange of contrast agent (driven by concentration differences between them) between the plasma and the body extravascular extracellular space (EES), which can be approximately modelled as a single lumped compartment; and 2) clearance of the contrast agent from the plasma by the kidneys, reflected by the glomerular filtration rate (GFR). The kinetics of the myocardial EES contrast agent concentration will then be predominantly determined by exchange of contrast agent between the plasma and the myocardial EES, initially again modelled as a single lumped compartment. We will also assume that the contribution of the exchange of contrast agent with the myocardium to the overall plasma concentration changes is small, relative to the exchange with the total body interstitial fluid pool, and so we will not model that component explicitly. These assumptions can be represented as a three-compartment model of the contrast agent exchange , as suge, and fractional plasma volume of the myocardium, vp, were derived from published MRI myocardial perfusion studies [p, can be taken from standard physiology texts, as can estimates of EES volume per unit body weight, Ve, hematocrit, Hct, and GFR, although there is a range of “standard” values given in the literature, and they will depend on age, sex, and body habitus; conventional estimates of blood volume per unit body weight, Vb, tend to be ~ 75 mL/kg. A value for permeability coefficient of the body capillaries per unit body weight, K, can then be calculated from the formula for m1 in Eq. 1 cited above from [p and Ve. The resulting set of initial values for the model parameters is shown in Table Initial estimated normal values for permeability-surface area product of the capillaries per unit tissue volume, PS, fractional volume of the myocardial EES, v studies  and norm studies . Serial  studies , 8. Estiove from , using tp, using Eq. p and Ve, at a rate that depends on K. Renal clearance of the contrast agent will lead to a further decrease in the plasma concentration, at a rate dependent on the GFR and the combined volume of plasma and the EES. The associated model parameters can thus be systematically used to adjust the model predictions so as to get a good fit to the observed plasma concentration–time course data. We can take advantage of the different effects of particular parameter value changes on different parts of the time course, in order to partially separate the process of fitting the different parameters associated with the serial plasma concentrations. As the exchange of contrast agent between the plasma and the myocardium is assumed to make a relatively negligible contribution to the overall plasma concentration time course, we can leave these initially adjusted parameter values, associated with the serial plasma concentrations, unchanged while we then adjust the parameters associated with the myocardial contrast enhancement. Again, we can take advantage of the different effects of changes of the different parameter values on different parts of the predicted curves to reduce the number of adjusted values that need to be explored to get a good fit with the data.Although there are a relatively large number of potentially adjustable model parameters, and relatively few data available to constrain them, we can systematically approach the adjustment of their values to fit the model predictions to the observed relaxation times (and their associated contrast agent concentrations), in order to effectively minimize the number of degrees of freedom to be explored at each stage in the fitting process. Extrapolating the observed plasma contrast agent concentration back to the time of the initial bolus injection of contrast agent, before there has been time for any significant exchange of the contrast agent with the EES, allows us to estimate the size of VIn order to make the distribution of the contrast agent within the myocardium more visually apparent in CMR, the associated LGE images are usually acquired with increased T1-weighted image contrast, typically by using inversion-recovery imaging . In invees, and potentially a smaller fractional blood volume, vbs. For example, Pack et al. [The ability to use LGE imaging is one of the strengths of CMR. While not very specific, it is a relatively sensitive way to demonstrate the presence of a wide range of myocardial abnormalities, including post-infarction necrosis and fibrosis, inflammation, infection, interstitial infiltration, and tumor. The basic mechanism of the relatively increased concentration of conventional contrast agent in abnormal myocardium (which leads to the appearance of LGE in the images) is generally considered to be the presence of an expanded extracellular space into which the contrast agent can diffuse, with an associated slowed rate of clearance of the contrast agent from that space , 13. Howk et al.  found exk et al.  found exk et al. , 16. Notk et al.  has showThe typical changes observed in the contrast enhancement dynamics in cardiac amyloid , relativThe qualitative recognition of the typical appearance of the characteristic LGE pattern in cardiac amyloid  can be used clinically to suggest the presence of cardiac amyloid, when examining CMR images. However, correlation of the CMR appearance with the findings on myocardial biopsy, when available, can sometimes reveal both “false positive” diagnoses, with multiple negative myocardial biopsies found when looking for the presence of amyloid suggested by the CMR appearance, and “false negative” diagnoses, with only nonspecific imaging findings in CMR of patients who are later found to have cardiac amyloid on myocardial biopsy. We can use the computer model of contrast agent kinetics to assess the likely contributions of some clinical factors to such atypical CMR appearances of cardiac amyloid.b to time t = 0, allows us to estimate Vp with Eq. b ~ 0.1 mL/kg; analysis of corresponding blood T1 data from [b. We kept this value for Vb fixed during the subsequent adjustments of the other model parameters.Figure ata from  leads toe by a factor of 0.6, to 0.09, brings the simulated blood T1 into good agreement with the later data values, as well  and in the myocardial EES (characterized by ve); the exchange of contrast agent between these spaces is characterized by PS of the myocardium, PSm. The contrast agent concentration in the myocardial plasma space will just track the blood concentration, with its contribution to the total myocardial contrast agent concentration scaled by vp. Similarly, the contribution of the myocardial EES to the total myocardial contrast agent concentration will be scaled by ve; increasing ve will decrease the myocardial T1, for a given myocardial EES concentration, Cme. Thus, in order to lower the myocardial T1 curve calculated with the model, to better match the data, we will need to increase the size of the myocardial extracellular space and/or increase the contrast agent concentration in the myocardial EES. The size of the myocardial extracellular space in the model can be increased through some combination of raising ve and vb and lowering Hctm. Increasing the value of PSm will speed the initial entry of contrast agent into the myocardial EES, but it will also speed the later clearance from the myocardial EES as the plasma concentration drops. Empirically adjusting the relevant parameters for the myocardial enhancement to be vb = 0.15, ve = 0.17, PSm = 1.3, and Hctm = 0.24 gives a good fit to the control myocardium values in [While these parameter value adjustments have improved the fit of the simulations to the control blood T1 data, they have decreased the agreement of the myocardium T1 simulations with the corresponding observed T1 data extracted from Fig. alues in . While tes (to ~ 0.95); decreased the scar permeability-surface area product, PSs, (to ~ 0.4); decreased the scar blood volume, vbs, (to ~ 0.05); and increased the scar native T1, T1s0, to 1000 ms, as summarized in Table s; subendocardial myocardial T1 values from cardiac amyloid patients in Fig. s will increase the early entry of contrast agent into the scar, but will also speed the washout of contrast agent from it later. Adjusting the values of ve and vb can be used to adjust the scale of the curves, but they are limited by physical constraints to sum to less than 1.0. Also note that the observed data on subendocardial LGE in cardiac amyloid patients would also reflect the influence of contrast agent exchange with an altered body EES, which is not included in the adjustment of the modeling parameters related to the exchange with the myocardium alone.For initial simulation of the LGE dynamics of a typical myocardial enhancing “scar”, such as can result from prior myocardial infarction, we increased the corresponding value of the scar EES, vCorresponding calculations of the difference of the T1 of the blood, and the T1 of the normal and the simulated scar myocardium, are shown in Fig. b to better fit the initial values of the blood T1 data for the amyloid patients in [b = 0.115 . Keeping these values fixed, we then then further adjusted the value of Ve to better fit the full set of values of the amyloid blood T1, yielding an estimate of Ve = 0.13 , which reflects the expected generalized amyloid tissue deposition. To illustrate the sensitivity of the fitting process to the parameter values, blood T1 simulations for three values of Ve are shown in Fig. e (to ~ 0.75); and decreased the myocardial permeability-surface area product, PS (to ~ 0.32), as summarized in Table For simulation of the LGE dynamics of cardiac amyloid, we first adjusted the value of V to ~ 0.3, as summNote that the T1 value of the blood in the cardiac amyloid simulation is now very close to that from the reference  myocardium Fig. , with nuWhile we have demonstrated how a combination of expansion of the myocardial EES and the general body EES can jointly contribute to the characteristic MRI LGE appearance of cardiac amyloid, we can further use the LGE simulation program to investigate the likely causes of patients who are found to have the “characteristic” appearance of cardiac amyloid on MRI LGE imaging, without positive myocardial biopsy. In particular, any other conditions that would lead to similar changes in the size of the body or myocardial EES could have similar changes in the simulated contrast agent kinetics. We can also use the LGE simulation program to investigate the likely causes of cases where we fail to see the characteristic MRI LGE appearance in patients with a positive myocardial biopsy. In this case, this is likely just a reflection of the relative amount of amyloid deposition being too low to produce the degree of expansion of the body and myocardial EES needed to produce the “characteristic” MRI LGE appearance of cardiac amyloid, as is seen if we readjust the corresponding modified parameter values for cardiac amyloid to be closer to the initial values used for fitting normal enhancement dynamics.Although the basic factors contributing to the dynamics of LGE in CMR have long been well understood, they have not previously been incorporated into a specific computer model of the myocardial contrast agent kinetics. This interactive model of the dynamics of myocardial contrast enhancement provides insight into the relative roles of different factors contributing to the qualitatively different kinetics of contrast enhancement seen in normal myocardium, scar, and cardiac amyloid, as well as some estimates of the values of the associated model parameters in these different cases. Although the model is necessarily a simplified representation of the underlying physiology, it captures some of the major features seen in clinical practice, and is able to approximately reproduce their expected quantitative scales. Although here we have focused on the use of the model for studying the dynamics of myocardial late gadolinium enhancement in cardiac amyloid, it would also potentially be readily adapted for modeling the contrast enhancement dynamics of other organs and other disease states.Attempts to calculate specific values of the relatively large number of model parameters from curve fitting of the observed contrast kinetics are likely to be somewhat unreliable, due to the generally ill-posed nature of such “curve stripping” and the under-constrained situation in this case, with only 4 key parameters being potentially available from the biexponential plasma concentration curves and two more parameters from the triexponential tissue concentration curves. However, the systematic approach that we have taken here to the parameter fitting allows us to focus on the fitting of only a few parameters at a time, which helps to constrain and stabilize the fitting process.The model was able to qualitatively reproduce the observed data on kinetics of contrast enhancement from , with reWhile we did not have comparable data on dynamic enhancement of myocardial fibrotic scar to work with, the model was able to capture the overall behavior of the endocardial enhancement in the cardiac amyloid patients, which would be expected to be qualitatively similar to other kinds of LGE. Interestingly, although the overall scale of the enhancement could be modeled well, the detailed shapes of the curves of the early and late phases of the subendocardial enhancement over time were not able to be fit as well, suggesting that the assumption of a “well-stirred” tissue interstitial space may not be fully adequate for modeling LGE dynamics in abnormal myocardium, as is discussed further below.The principal aim of this work was to better understand the origins of the distinctive features of the LGE dynamics observed in many cases of cardiac amyloid: 1) diffuse (and somewhat weak) subendocardial LGE, and (2) a relatively dark appearance of the blood in PSIR images, through using the model for fitting of the contrast enhancement data in [ diffuse D, and the local concentration gradient, as per the Fick diffusion law [t is on the order of 2/4D. Although we do not have a specific value for D of contrast agents like Gd-DTPA in myocardial interstitium, we can use an estimated value of D on the order of 2 × 10–4 mm2s−1, [D, and thus to correspondingly increase the associated diffusion time and further prolong the contrast agent clearance phase. Replacing the simple “well-stirred” myocardial EES model with a catenary two-component model (Appendix 4) improves the agreement of the predicted and observed contrast enhancement dynamics.Although the scale of the myocardial enhancement in cardiac amyloid could be modeled fairly well, the detailed shapes of the early and late phases of the myocardial enhancement were not able to be fit as well, suggesting that the assumption of a “well-stirred” tissue interstitial space may not be fully adequate for modeling LGE dynamics of abnormal myocardium with an expanded tissue EES. The role of diffusion of contrast agent within an expanded tissue interstitial space may not be fully captured by simply decreasing the effective value of the PS of the capillary-EES interface in the model. In particular, if the time scale for diffusion of contrast agent within the interstitium is on the order of or longer than the time scale for changes in the plasma concentration, rather than the EES effectively being a simple “well-stirred” compartment, spatial gradients of contrast agent concentration may develop within the interstitium, around the capillaries . In the sion law . If the  mm2s−1, , 25, 26;Although the model was able to reproduce the distinctive features of LGE in cardiac amyloid well, not all patients with cardiac amyloid have these features in their CMR images. As suggested in , this isThis study was performed retrospectively, using previously published data from patients who had had both conventional CMR and T1 mapping; thus, there may be associated selection biases in the results.While we used a well-established three-compartment pharmacokinetic model of MRI contrast enhancement  to calculate the myocardial contrast enhancement dynamics, there are simplifications associated with the model that could limit the reliability of the results, such as neglecting the possibility of diffusion-related concentration gradients in the tissue interstitial space, which is here assumed to be “well-stirred”. Extending the model to a catenary model of the myocardial EES can improve the results.The presence of multiple potentially competing effects of the different underlying physiology changes, and the limited data available to characterize them, makes it difficult to assign levels of importance to the relative contribution of these different factors in the observed dynamics. However, we have used a systematic approach to the fitting of the model parameter values, to try to reduce the confounding effects of having multiple parameters to be fit.e and vmb.The fitted parameter values were adjusted to match the observed enhancement dynamics of control (hypertensive) subjects rather than truly normal subjects. Thus, although they “had no other cardiovascular abnormality from the clinical history and examination or by CMR” , they maA three-compartment model of the dynamics of myocardial contrast enhancement in magnetic resonance imaging is able to capture the qualitative features of late gadolinium enhancement (LGE), in both control subjects and patients with cardiac amyloid. In particular, the characteristic “dark blood” appearance of PSIR images of LGE in cardiac amyloid is seen to likely primarily reflect expansion of the extravascular extracellular space (EES) by amyloid in the “reference” myocardium. The altered cardiac amyloid contrast kinetics also reflect expansion of the body EES.Additional file 1. LGE_sim_catenary.mlapp. MATLAB program for interactive simulation of contrast enhancement dynamics.


Ischemic heart disease is the leading cause of mortality worldwide. In this context, myocardial viability is defined as the amount of myocardium that, despite contractile dysfunction, maintains metabolic and electrical function, having the potential for functional enhancement upon revascularization. Recent advances have improved methods to detect myocardial viability. The current paper summarizes the pathophysiological basis of the current methods used to detect myocardial viability in light of the advancements in the development of new radiotracers for cardiac imaging. Ischemic heart disease is the leading cause of mortality worldwide and is responsible for 8.9 million global annual deaths . PatientFurthermore, for patients with ischemic cardiomyopathy, the question is not whether they have viable myocardium but how much they have of each type, where it is, whether it is likely to recover and how long this may take. Central to this is the need for multidisciplinary collaboration to integrate, even with the help of machine learning, clinical information with the myocardial and coronary substrate and imaging data. Noninvasive methods for detecting viability, including echocardiography, cardiac MR and perfusion computed tomography (CT), and nuclear medicine techniques such as single-photon emission CT (SPECT) and positron emission tomography (PET) are rapidly evolving ,13,14,15201Tl and 99mTc-sestamibi has a respectable indication to evaluate myocardial viability [13N-ammonia, 82Rb, or 15O-water and for myocardial viability studies by using radiolabeled 18F-2-deoxy-2-fluoro-D-glucose (FDG)  has been demonstrated . Despiteiability . Its useiability . PET is se (FDG) . 18F-FDGrization . Current18F-FDG [Recurrent episodes of transient post-ischemic dysfunction  due to ischemia and reperfusion not so severe or so long as to cause myocellular necrosis as well as a chronically reduced perfusion can initiate a protective state of myocardial down-regulation called “myocardial hibernation”. This is an advanced state of ischemic dysfunction, histologically characterized by myocellular dedifferentiation, change in gene expression, losses of the contractile proteins and alterations of myocardial metabolism, which starts to prefer the use of glucose instead of free fatty acid, with energy production mainly depending on anaerobic glycolysis ,14. Thes18F-FDG .18F-FDG tracer is based on intracellular trapping after phosphorylation because it produces a substrate that is not useful for metabolism but is helpful to detect metabolic cellular changes during ischemia. The imaging evaluation is realized by a semiquantitative method based on comparatively regional uptake of 18F-FDG [18F-FDG tracer can be used to investigate metabolism, perfusion imaging  is commonly realized using 13N ammonia or 82Rb tracers. In hypoperfused and dysfunctional myocardium, it is possible to identify cell survival and viability in the presence of 18F-FDG uptake in the same territory (flow-metabolism mismatch) or not viable tissue in case of not-detectable 18F-FDG uptake (flow-metabolism matched defect) [82Rb/18F-FDG PET imaging are depicted in The clinical applicability of  18F-FDG . To inve 18F-FDG . While 1 defect) . Represe18F-FDG activity in the septum with normal perfusion due to a left bundle branch block [18F-FDG administration requires patient preparation  to stimulate endogenous insulin release and to minimize the variability in substrate setting between patients. After glucose load, insulin can be administered as needed [11C-acetate PET tracer. The reduction in this tracer uptake can be related to a necrotic area in patients with recent myocardial infarction [11C has been considered a promising candidate to investigate myocardial viability by PET scan. Its uptake and its metabolism can be related to perfusion, oxygenation levels and neurohumoral environment fitting for cardiac metabolism studies. Nevertheless, the difficult washout limited the routine use of this tracer in clinical practice [15O-water has been also proposed considering the concept that the injured myocardial regions have a reduced capability to provide rapid water exchange. This method, interesting but hardly feasible, is reserved for medical centers equipped with a cyclotron due to the very short 15O radionuclide half-life of 120 s. Regarding this tracer, an excellent study was carried out by Grönman et al. [Of note, a potential further pattern can be observed with reversed perfusion-metabolism mismatch when there is a reduction in ch block . The comch block . Howevers needed . Many sts needed ,32,33. As needed . Howevers needed . Conversfarction . Free fapractice . To inven et al. . In a pi201Tl can be used to differentiate between viable and nonviable myocardium [201Tl is driven by the coronary blood flow state at rest whereas the later uptake over the next 4–24 h is determined by the tracer redistribution, depending on cellular membrane integrity. Hibernation may appear as a myocardial perfusion defect on initial imaging due to reduced coronary blood flow at rest but normalizes on the delayed imaging (with or without 201Tl reinjection) from redistribution of the tracer. The sensitivity of viability detection by 201Tl imaging may increase in the late (24 h) reinjection/redistribution protocol compared to the 4 h early redistribution protocol. The radiopharmaceutical activity of 201Tl in rest/redistribution imaging is approximately 3 mCi with a corresponding radiation effective dose of 10–15 mSv. The uptake into the myocyte happens by the Na+/K+-adenosine triphosphate transport system and by facilitative diffusion, too [201Tl retention requires a whole sarcolemma. The redistribution starts about 15 to 20 min after injection. Watching thallium uptake, retention, and redistribution, using the two main protocols (rest- and stress-redistribution) for myocardial perfusion, sarcolemma membrane function and myocyte metabolic activity to identify myocardial viability can be investigated [201Tl injected just before peak exercise or at peak pharmacologic vasodilatation. Stress imaging is obtained 15 min after administration. If a fixed perfusion defect is noted, the redistribution images are obtained after 24 h from tracer injection [201Tl imaging to predict recovery of left ventricular function after coronary revascularization [99mTc-labeled tracers (sestamibi and tetrofosmin), are commonly used in the evaluation of ischemia; they can also be used in the same protocols to assess myocardial viability. 99mTc is a lipophilic substrate, it enters in myocytes by passive diffusion. Differently from 201Tl, the redistribution of 99mTc is limited. Uptake and retention of 99mTc require intact mitochondrial and sarcolemma membranes, which reflect myocyte viability. 99mTc sestamibi has been shown to be comparable to 201Tl in its ability to predict regional recovery of function following revascularization [99mTc-labeled tracers cannot be considered ideal tracers given their relatively low first-pass extraction fraction and high liver absorption, although they boast low lung extraction. Conversely, the advent of ultrafast high-sensitivity gamma cameras paved the way to evaluate potential novel probes with high initial absorption of the heart, combined with longer myocardial retention and high heart/background ratios such as 99mTc-Teboroxime [99mTc-sestamibi may expand sensitivity [201Tl to detect reversible left ventricular dysfunction [201Tl and sestamibi imaging [123I to study acute myocardial infarction [123I-BMIPP imaging may produce three different situations: defects of both perfusion and fatty acid metabolism imaging, representing scar or nonviable tissue; lower 123I-BMIPP uptake compared to perfusion tracers’ distribution implicating metabolically damaged but viable myocardium; normal uptake of both perfusion and metabolic tracers meaning healthy myocardium. Identification of these perfusion-metabolism correlations helps to detect viable and nonviable myocardium [123I-BMIPP and 99mTc-labeled perfusion tracers is lower than the combined imaging by perfusion SPECT and 18F-FDG PET imaging studies. Thus, the latter method is preferred [ocardium ,38. Thision, too . 201Tl rstigated . For thenjection . A meta-rization . 99mTc-lrization ,43. Howeboroxime . It has sitivity ,46. The function . Moreove imaging . Knowledfarction ,50,51. Cocardium . Howeverreferred .68Ga is a useful peptide for PET scan, with a selectively increased binding in presence of a C-C chemokine receptor type 2 (CCR2) ligand [68Ga-DOTA-ECL1i has been recently investigated to track the recruitment, accumulation and resolution of CCR2+ monocytes and macrophages in the injured myocardium in a mouse model, demonstrating its capacity to identify inflammation involving both the infarct and peri-infarct areas [68Ga-FAP inhibitor development [68Ga-FAP inhibitor, and it can be used to investigate myocardial conditions associated with fibroblast activation [18F-labeled tetraphenylphosphonium. This method was used for the quantitative mapping of total membrane potential in swine myocardial cells [123I-meta-iodo benzyl-guanidine (123I-MIBG) and PET studies by using different innervation tracers such as 18F-Flubrobenguane , 18F meta-fluorobenzylguanidine (18F-MFBG), or 11C-hydroxyephedrine (11C-HED) [23I-MIBG imaging may count on a robust body of literature including large clinical trials, and it boasts widespread availability of the tracer around the world, the lower resolution of gamma cameras as compared with PET scan may represent a limitation. At the same time, 11C-HED PET/CT imaging benefits from the implied advantages of the scan, such as higher temporal and spatial resolution, making possible absolute quantification. However, the short radionuclide half-life requires on-site production of the compound. Yet, the utilization of 18F-labeled sympathetic molecules may overcome this limitation [68Ga has been reported [The strength of PET as an imaging technique relies on the versatility of positron-emitting radionuclides that can be integrated into important biochemical molecules. Not only can the distribution of these molecules be imaged, but their uptake can be quantified. In this way, it is possible to assess myocardial perfusion, glucose utilization, fatty acid uptake and oxidation, oxygen consumption, contractile function and presynaptic and postsynaptic neuronal activity . Using s) ligand ,59. Cellct areas . Other sct areas . There act areas . The perct areas . Unfortuelopment  because elopment . A high elopment . Fibrobltivation ,67. Recetivation . The mittivation . A changtivation . Alpert,tivation  introducal cells . In a foal cells  confirmeal cells . Of noteal cells . Based o11C-HED) ,75. An emitation . This mareported . This isreported . Table 4In the time of personalized medicine, the identification of methods that break down technical and clinical limitations is the new challenge. In the context of research for innovation in cardiovascular imaging, a potential breakthrough could be represented by new tracer development to assess myocardial viable tissue with the ability not only to improve diagnostic performances but also to refine the current knowledge on myocardial viability physiological and pathophysiological patterns.


Right ventricle infarction (RVI) is predominantly a complication of inferior wall myocardial infarction; it occurs in approximately one third of these patients. Right ventricular dysfunction in patients with inferior STEMI and RV infarction was under assessed. Nevertheless, studies which targeted RV assessment by echocardiography, did not routinely evaluate RV diastolic dysfunction. In this study, we aimed to evaluate RV diastolic dysfunction and its prognostic value in patients with inferior STEMI and RVI.p value of 0.015.Sixty patients with inferior STEMI and RV infarction, who underwent primary PCI were enrolled in the study. Patients with pre-existing clinical conditions that might affect RV function, were excluded. Echocardiography was performed within twenty-four hours following the PCI, to assess the RV systolic and diastolic functions with special focus on tricuspid inflow velocities  by pulsed wave (PW) doppler and tricuspid annular velocities by tissue doppler index (TDI) . Clinical features and MACE, including cardiogenic shock, arrhythmia, stroke, reinfarction and death were analyzed in all our patients within 3 months follow up period. The average age of the study population was 51.58 ± 10.11 years, 10% were females. Five patients developed MACE , of whom four occurred in hospital within the first 48 h. Patients who developed MACE had high filling pressures, as all of them had E/E′ > 6. E′ velocity ≤ 6 cm/sec was associated with increased MACE as 25% of patients with E′ velocity ≤ 6 had MACE compared with 2.3% of patients with E′ velocity > 6 with a Tricuspid annular velocities by TDI are essential when evaluating RV diastolic dysfunction. E/E′ and E′ velocity have a prognostic value in patients with inferior STEMI and RV infarction; E/E′ > 6 and E′ velocity ≤ 6 cm/sec were associated more MACE in patients with inferior STEMI and RVI. Patients with inferior ST-elevation myocardial infarction (STEMI) have more favorable prognosis than patients with anterior STEMI, although certain associations may indicate a worse outcomes and increased mortality. High risk groups of inferior STEMI patients are those with heart block, right ventricle (RV) infarction, cardiogenic shock and cardiac arrest due to ventricular tachycardia or ventricular fibrillation. Right ventricle infarction is predominantly a complication of inferior wall myocardial infarction (IWMI); it occurs in approximately one third of these patients. In about one half of patients with RV infarction, it is of hemodynamic significance. RV infarction is associated with anterior myocardial infarction in less than 10% of cases; isolated RV infarction is rarely seen . PatientThere is still little information regarding RV diastolic function & numerous gaps remain in our understanding. In ischemic patients, the pathophysiologic response is a failure of the early rapid filling to increase and a heightened dependency on atrial contribution and consequent elevated right atrial (RA) pressure, marked diastolic dysfunction with elevated filling pressures occurs in case of acute RV myocardial infarction –7.Marked diastolic dysfunction with elevated filling pressures occurs in case of acute RV myocardial infarction. RV diastolic dysfunction serves as an early and more easily quantifiable marker of subclinical RV dysfunction. Multiple studies have shown that RV diastolic dysfunction is usually present before apparent systolic dysfunction and before RV dilatation or RV hypertrophy (RVH). Tricuspid annular velocities are higher than the mitral annular velocities. E/E′ ratio can be used to estimate RV filling pressures & diastolic function, RV E/E′ ratio greater than 6 suggests a RA pressure greater than 10 mmHg , 8–10.Evaluation of RV diastolic function and its prognostic value in patients with RV infarction in the setting of inferior STEMI.Patients, who were admitted with Inferior STEMI and RV Infarction to two tertiary hospitals  between October 2019 and December 2020, were enrolled in this prospective study. The diagnosis was established on clinical basis, enzyme changes, 12-lead electrocardiogram (ECG) and Echocardiography. The inclusion criteria were: (a) Onset of symptoms < 24 h before Primary PCI; (b) ST-segment elevation > 0.1 mV in two contiguous inferior leads, II, III, or aVF, and ST-segment elevation > 0.1 mV in V3R or V4R.; (c) Right coronary artery occlusion proximal to the major right ventricular (RV) branches at base line coronary angiography; (d) All patients who were treated with primary PCI. Exclusion criteria were: (1) Patients with concurrent pericardial disease; (2) Atrial fibrillation on admission; (3) Previous history of RV dysfunction; (4) Previous history of chronic pulmonary disease, pulmonary hypertension or acute pulmonary embolism; and valvular heart disease (moderate or severe insufficiency and/or stenosis).Following admission, all patients were subjected to full history taking, clinical examination, blood sampling including cardiac enzymes, ECG, PPCI and echocardiography.RV infarction was diagnosed clinically by hypotension (defined as systolic blood pressure below 90 mmHg lasting more than 15 min), clear lungs, and elevated Jugular venous pressure.All patients received dual antiplatelets , and parenteral anticoagulants and PPCI was performed in accordance with ESC guidelines of myocardial revascularization   was recorded.We divided our studied patients to two groups: MACE patients and non-MACE patients; we compared between these groups according to demographic data, risk factors and echocardiographic parameters.t-test was used to compare two groups for normally distributed quantitative variables, while Mann–Whitney test was used to compare between two groups for abnormally distributed quantitative variables. Positive correlation tests using ROC curve and AUC were used to estimate the cut off value for E′ velocity that is correlated to MACE. p value less than 0.05 was considered significant.Data were fed to the computer and analyzed using IBM SPSS software package version 20.0. . The Kolmogorov–Smirnov was used to verify the normality of distribution of variables. Comparisons between groups for categorical variables were assessed using Chi-square test, Fisher’s Exact or Monte Carlo correction were used as a correction for chi-square when more than 20% of the cells have expected count less than five. Student's p-value of 0.020  were females. The average age of the study population was 51.58 ± 10.11 years. Regarding significant demographic data, adverse events were more common in females. Five patients out of the enrolled 60 patients developed MACE  and stroke). Ninety percentage of MACE developed in the hospital in the 48 h following the admission. Forty percentage of MACE group were females compared to 7.3% in the non-MACE group with a significant 0% were fp = 0.003), 40% compared to 89.1% in non-MACE patients. Hundred percentage of MACE group had diabetes (DM) (p = 0.001), 60% had chronic kidney disease (CKD) (p = 0.003), and 80% had dyslipidemia (p = 0.045). Also, LDL was significantly higher in patients who had MACE (p = 0.015) , only 10 patients showed 0.1 mV ST segment elevation in V1, and 5 patients showed ST segment elevation in posterior leads.PCI procedure: All patients (100%) received oral dual antiplatelets (DAPT) before the procedure. Forty patients (66.66%) received ticagrelor and the other 20 patients (33.34%) received clopidogrel. Regarding the pain to balloon time: primary PCI was performed within 24 h from onset of chest pain, and the culprit lesion was proximal RCA occlusion  in all patients.p value 0.027. As regards the RV systolic function, it was significantly lower in MACE group as fractional area change (FAC) ranged from 23 to 40% with a mean of 29.0 ± 7.31% compared to non-MACE group ranging from 20 to 50% with a mean of 37.91 ± 6.97% (p = 0.008). IVC diameter and pulmonary artery systolic pressure (PASP) were higher in MACE group, but not statistically significant.Echocardiography Table : RegardiFor the PW velocities Table : PW velop = 0.007). A′ and S′ velocities were not statistically significant between all groups.Regarding the TDI (tissue doppler imaging) velocities Table , E′ velop = 0.015) .We also analyzed the relation between E and E′ and the occurrence of MACE Table , we clasWhen reviewing the literature, many studies are found discussing RV systolic function and fewer discussing the RV diastolic function. RV diastolic function interpretation is very difficult and challenging. RV diastolic function is affected by respiration, circulating volume in intravascular spaces, LV function and filling pressures, preexisting pulmonary hypertension, and ventricular interdependence , 9. RV dThe parameters used to assess RV diastolic function are essentially the same as those used to assess the left side: Doppler velocities of the Trans tricuspid flow , tissue Doppler velocities of the tricuspid annulus  and deceleration time. The tricuspid E/E′ ratio is highly recommended to accurately assess RV diastolic function  Trans-trIn our study, we included 60 patients with inferior STEMI and RV infarction. All of them were treated by PPCI. Females were less represented (10%). Smoking was the most common risk factor, 51 patients (85%) were smokers, but most reports showed that only 40–45% of STEMI patients were recent smokers. Despite this increased prevalence, there was no difference in the outcomes between smokers and nonsmokers. The studied population has an increased prevalence of smoking in comparison to other populations . All of p value of 0.048.According to ASE guidelines for assessment of right heart in adults, the tricuspid E/E′ ratio has been shown to correlate well with hemodynamic parameters. We used tissue doppler and other parameters, e.g., IVC collapsibility to identify patients with high filling pressures , 12. ThiRestrictive pattern of RV diastolic function by PW doppler (E/A ratio > 2 and DT < 120), was absent in our cases. The single case showed this pattern was excluded due to frequent PVCs (bigeminy). No cases in our study showed this pattern even in the presence of RV systolic dysfunction or LV diastolic dysfunction grade 3 (LV restrictive pattern does not necessitate severe RV diastolic dysfunction). By reviewing the literature, most of studies diagnosed RV severe diastolic dysfunction (DD) by right heart catheterization. They did not rely on PW doppler for DD diagnosis. Mertens et al. studied indices of right ventricular (RV) diastolic function in patients with tetralogy of Fallot (TOF). The purpose of this study was to determine echocardiographic predictors of severe RV diastolic dysfunction by comparing the following indices , and hepatic vein diastolic flow reversal (HVDFR) with the results of right heart catheterization. Of the indices assessed, dilated IVC had the best sensitivity of 95% while HVDFR had the best specificity of 69% for detecting severe RV diastolic dysfunction . Also, Kp value 0.015. Screening of patients by E′ may be useful in anticipating MACE.As E/A ratio, E velocity and A velocity by pulsed wave doppler on right side vary significantly with respiration and fluid status, tissue doppler is a better alternative. The less the E′ velocity, the higher the incidence of MACE. E′ may be the only indicator of severe RV diastolic dysfunction. What is the cutoff point? In our study it was 6 cm/s. We classified the patients into two groups, first group E′ is less than or equal to 6 (≤ 6) and the other E′ > 6. The group with E′ ≤ 6 was associated with increased MACE in comparison to the group with E′ > 6 with a statistically significant MACE developed in 5 patients of which 4 patients complicated during hospital stay. B Altıntaş also reported that all the MACE in his study developed during the hospital stay We performed our echocardiography study within 24 h following the PPCI. We considered it unethical to delay the PCI of patients with myocardial infarction to perform a complete echocardiography study before, so we do not know the RV diastolic function at the time of admission or before successful reperfusion.In our study, one patient died of arrhythmia (AF) and stoke. By reviewing the past articles of IWMI , RV infarction was associated with increased arrhythmia in comparison to cases of IWMI without RV infarction . Female There is still little information regarding RV diastolic dysfunction (DD) and its grading in patients with RVI. Marked diastolic dysfunction with elevated filling pressures occurs in case of acute RV myocardial infarction. RV DD serves as an easily quantifiable marker of RV dysfunction and can be used for its prognostic significance in patients with inferior STEMI and RV infarction. Tissue Doppler in the evaluation of RV DD is inevitable. In our study, E′ < 6 cm/sec and E/E′> 6 were associated with increased MACE. E′ and E/E′ should be routinely used during the evaluation of the right ventricle in cases of RV infarction.Small number of included patients.Strain imaging was not performed in the included patients.No MRI or right heart catheterization to verify or compare our results.