What are the main findings?This study demonstrated that ultrasound-facilitated catheter-directed fibrinolysis for the treatment of 45 patients with intermediate high-risk pulmonary embolism was associated with significant improvements in hemodynamics and low major bleeding events as demonstrated in previous trials (Ultima and Seattle II). However, this protocol used a lower dose and shorter duration of t-PA. The third arm of Optalyse PE-Trial used the same regime (6 mg/6 h/lung) for the treatment of 24 patients.It focuses on pulmonary artery hemodynamics as a primary precise surrogate marker for therapy effectiveness in addition to RV/LV ratio that was used in previous trials (Ultima and Seattle II), which has a bias of interobserver variability.What is the implication of the main finding?It assessed pulmonary artery hemodynamics for the first time by fibrinolysis delivery catheter, without additional need for a right heart catheterization. The results matched the right heart catheter results in EKOS and Heparin arm of Ultima trial, thereby confirming the validity of these diagnostic tools.It’s a valid and precise diagnostic tool to assess therapy effectiveness and reduce additional procedure-related complications, hospital residency, and economics. It gives this therapy additional diagnostic potential. It stressed the importance of interdisciplinary teams in the management of PE and evaluated the quality of life of these patients. This protocol shortens ICU stay to 6 h.p < 0.001). The mean RV/LV ratio decreased from 1.2 ± 0.85 at baseline to 0.85 ± 0.12 at 48 and to 0.76 ± 0.13 at 90 days (p < 0.001). Five patients (11%) died within 90 days of therapy. Conclusions and Highlights: Pulmonary artery hemodynamics were assessed using a delivery catheter for fibrinolysis, which is reproducible for identifying PE at risk of adverse outcomes. The results matched the right heart catheter results in EKOS and Heparin arm of Ultima trial, thereby confirming the validity of this potential diagnostic tool to assess therapy effectiveness and thereby reduce additional procedure-related complications, hospital residency, and economics. These results stress the importance of having an interdisciplinary team involved in the management of PE to evaluate the quality of life of these patients and this protocol shortens ICU admission to 6 h.Background: Ultrasound-facilitated and catheter-directed low-dose fibrinolysis (EKOS) has shown favorable hemodynamic and safety outcomes in intermediate- to high-risk pulmonary embolism (PE) cases. Objectives: This prospective single-arm monocentric study assessed the effects of using a delivery catheter for fibrinolysis as a novel approach for acute intermediate- to high-risk patients on pulmonary artery hemodynamics PE. Methods: Forty-five patients (41 intermediate–high and 4 high risk) with computer tomography (CT)-confirmed PE underwent EKOS therapy. By protocol, a total of 6 mg of tissue-plasminogen activator (t-PA) was administered over 6 h in the pulmonary artery . Unfractionated heparin was provided periprocedurally. The primary safety outcome was death, as well as major and minor bleeding within 48 of procedure initiation and at 90 days. The primary effectiveness outcomes were: 1. to assess the difference in pulmonary artery pressure from baseline to 6 h post-treatment as a primary precise surrogate marker, and 2. to determine the echocardiographic RV/LV ratio from baseline to 48 h and at 90 days post-delivery. Results: Pulmonary artery pressure decreased by 15/6/10 mmHg ( Pulmonary embolism (PE) is the third most common cardiovascular cause of death, after myocardial infarction and stroke. The annual incidence is increasing  [Risk stratification to identify intermediate- and high-risk PE is of paramount significance due to the increased mortality of up to 30% in these groups, according to the European Society of Cardiology—Guideline 2019 [The advanced treatment options used for PE vary by institution, medical specialty, and operator experience . AdditioTreatment modalities of thrombotic pulmonary embolism include anticoagulation, intravenous or catheter-directed thrombolytic therapy, catheter-directed mechanical thrombectomy, and surgical embolectomy.Due to its favorable hemodynamic results in comparison to anticoagulation alone and superior safety outcomes compared to systemic fibrinolysis, the use of ultrasound-facilitated and catheter-directed low-dose fibrinolysis ) could be a reasonable treatment modality in intermediate- and high-risk pulmonary embolism. The results of improvement in hemodynamic effects and favorable safety have been shown in Ultima study . EKOS thIn Vitro investigation ultrasound separates fibrin strands, enhancing the penetration of the thrombolytic agent into the emboli . In thisThis article discusses a prospective single-arm monocentric cohort study conducted to evaluate the hemodynamic effect of EKOS using a delivery catheter for fibrinolysis for the first time as a new approach for measuring pulmonary artery pressure for acute pulmonary embolism. This can improve our understanding of invasive and noninvasive hemodynamic measurements as well as outline the safety outcomes of EKOS therapy and the possibility to combine these data with other interventional modalities, thus influencing current practice and guidelines.n = 18 (29), with screening failures due to life expectancy < 3 months (n = 2), increased risk of bleeding (n = 11), patient not giving consent (n = 4), and pregnancy (n = 1)), and enrolled 45 in this prospective single-arm study of ultrasound-facilitated and catheter-directed low-dose fibrinolysis ”. Thus, least 40 should be included. The sample size was calculated for a one-sample t-test (one-sided): H0mu = 0; H1: effect = 3.2; standard deviation = 7.8; power: 80%.The Ultima study  reportedt test or Wilcoxon signed rank test. For two-group comparisons, a two-sample t test or Wilcoxon rank sum test was used for continuous data, and the Fisher exact test was used for binary data. All reported p values were two-sided, and a p value < 0.05 was considered statistically significant. An intercept-only mixed model repeated-measures analysis was conducted, changing the RV/LV diameter ratio, and TAPSE and systolic pulmonary artery pressure were measured indirectly in the echocardiography as the dependent variable. The results were adjusted for the logarithm of NT-Pro-BNP at baseline; p values were not adjusted for the multiplicity of comparisons between different points in time, as there were just two or three time points.The results for continuous variables were compared with baseline using a paired p-values with the Bonferroni–Holm correction were used. All statistics were determined using jamovi version 1.6 statistical software retrieved from “https://www.jamovi.org (accessed on 26 May 2022)”.To compare all measurement times simultaneously, ANOVA or the Friedman Test with multiple post hoc comparisons was performed. To assess the statistical significance of single comparisons, All statistical calculations were performed using the statistical software package SPSS (Version 28).An intermediate–high risk of PE (Simplified Pulmonary Embolism Severity Index (sPESI) ≥ 1, RV strain, positive cardiac markers);High risk of PE ;Intermediate–low risk of PE with deterioration of symptoms or hemodynamics .Patients were eligible to participate if they had the following:Ischemic stroke within three months;Active intracranial or intraspinal disease within 6 months;Major surgery within 7 days;Recent active bleeding from a major organ;Platelets < 50,000/mL;Pregnancy.Exclusion criteria were as follows:Anticoagulation was initiated with full-dose intravenous unfractionated heparin with a target-activated partial thromboplastin time (PTT) of 60 to 80 s. After completion of the procedure, all subjects received full anticoagulation. The drug, dose, frequency, and duration of anticoagulation were selected by the attending physician and according to the patient’s comorbidity.The EkoSonic Endovascular System  comprises three components: the Intelligent Drug Delivery Catheter, a removable MicroSonic device, and a reusable Eko-Sonic control unit. The procedure was performed by an experienced operator from interventional cardiology.Venous access was obtained via the common femoral route. After catheter placement and before the activation of the ultrasound and infusion of fibrinolytic therapy, baseline right and left pulmonary artery pressures were transduced through the catheters . BecauseSee Follow-up transthoracic echocardiography was performed within 48 h after initiation of the procedure to evaluate the changes in the RV/LV diameter, ratio, and RV function using tricuspid annular plane systolic excursion (TAPSE) and to estimate pulmonary artery systolic pressure noninvasively. Improvement in symptoms and hemodynamic assessment were recorded and analyzed by experienced cardiologists. Bleeding complications and safety outcomes were assessed up to 48 h after the procedure.Patients were scheduled for a 90-day follow-up clinical visit; the repeated echocardiography and assessment of the outcomes are detailed below.The primary efficacy was the mean difference in the right and left pulmonary artery pressures measured invasively using the fibrinolysis delivery catheter at baseline to 6 h after initiation of therapy in the intensive care unit.A secondary efficacy outcome was the difference in RV/LV diameter ratio, right ventricular function, and pulmonary artery systolic (measured noninvasively) from baseline to 48 h after the initiation of the procedure and at 90 days.The primary safety outcome was death, as well as major and minor bleeding within 48 h of the initiation of the procedure. Bleeding events were classified by the GUSTO  bleeding criteria . Severe The secondary safety outcome evaluated quality of life assessment using the German version of the EQ-5D-3L questionnaire .2) was consistent with an obese patient population. Common risk factors for PE included obesity (73%), hypertension (41%), immobility within 90 days of PE diagnosis (17%), chronic lung disease (20%), presence of deep vein thrombosis (DVT) (48%), chronic renal disease (11%), previous history of stroke (11%), present history of active cancer (22%), and hyperlipidemia (13%).The mean age was 66.7 ± 14.7 years . The meaAll patients had symptomatic PEs . The durThe mean total dose of t-PA was 6 or 12 mg . All   . The RV Procedural success was achieved in 100% of cases . The meaFour moderate bleeding events occurred with discharge after intervention without any residuals . It is dThis study demonstrated that ultrasound-facilitated and catheter-directed fibrinolysis for the treatment of 45 patients with intermediate- to high-risk pulmonary embolism was associated with significant improvements in hemodynamics and few major bleeding events, as demonstrated in previous trials (Ultima and Seattle II). However, this protocol used lower doses and a shorter duration of t-PA treatment. The third arm of Optalyse PE-Trial used the same regime (6 mg/6 h/lung) for the treatment of 24 patients.We focused on pulmonary artery hemodynamics as a primary precise surrogate marker for therapy effectiveness in addition to the RV/LV ratio that is used in previous trials (Ultima and Seattle II), as the latter has a bias in terms of interobserver variability.As the primary increase in pulmonary artery pressure influences secondary changes in the RV/LV diameter ratio, we used both parameters as surrogate markers for primary endpoints to assess the effectiveness of ultrasound-facilitated and catheter-directed low-dose fibrinolysis.This study evaluates the first-time use of fibrinolysis delivery catheters as a diagnostic as well as a therapeutic tool to assess the safety and effectiveness of this therapy.This resulted in no episodes of intracranial hemorrhage. There was one GUSTO -defined major bleeding event (2.2) and four GUSTO-defined moderate bleeding events (8.9). We observed a significant decrease in pulmonary arterial pressure by more than 30% at the end of the procedure using a fibrinolysis delivery catheter, and a significant 30% decrease in the echocardiographically assessed RV/LV diameter ratio over 48 h.(1)Precapillary pulmonary hypertension  ≥ 25 mmHg with a capillary pulmonary pressure ≤15 mmHg) assessed by right cardiac catheterization;(2)At least one segmental perfusion defect evident on ventilation scan/perfusion;(3)Signs of chronic thromboembolism on chest CT angiography or conventional pulmonary angiography  in patients receiving effective anticoagulation therapy for at least three months after a pulmonary embolism episode . A recenThe goal of this therapy is to restore reperfusion, decrease pulmonary artery pressure, recover RV function, and induce increases systemic perfusion, thereby improving symptoms and survival and preventing chronic thromboembolic pulmonary hypertension, which has its own comorbidities. In this study, we stress pulmonary artery pressure as a surrogate marker to predict and diagnosis this disease early. However, if CTEPH occurs, early detection is essential for optimal outcomes. The diagnostic criteria of CTEPH are as follows:In the European ULTIMA (Ultrasound Accelerated Thrombolysis of Pulmonary Embolism) trial of 59 patients with submassive PE, ultrasound-facilitated and catheter-directed low-dose fibrinolysis plus anticoagulation used a higher dose of t-PA (20 mg), demonstrated a 0% incidence of major bleeding, improved RV function with a 30% difference in the RV/LV ratio, and reduced pulmonary artery pressure (using right heart catheter) from baseline to 24 h to a greater extent than anticoagulation alone . In the The difference in the definitions of major bleeding in previous studies explains the variation in outcomes .Our study used a lower dose of t-PA (6 mg/lung/6 h). This regime was used in the third arm of the OPTALYSE PE trial for 24 patients, demonstrating that treatment with ultrasound-facilitated catheter-directed low-dose fibrinolysis using a shorter delivery duration and lower dose of t-PA (4–12 mg of t-PA for 2.6 h) had similar efficacy and better safety outcomes compared to higher doses  .In this study, as in the ULTIMA and Seattle studies, invasive hemodynamic measurements using fibrinolysis delivery catheter confirmed a significant reduction in pulmonary artery pressure and improvement of echocardiographic parameters after the completion of therapy. It is suggested that ultrasound-facilitated and catheter-directed fixed lower-dose fibrinolysis is similarly effective for reducing pulmonary artery pressure and improving echocardiographic parameters within 6 and 48 h, respectively, as compared to the higher-dose fibrinolysis used in the Ultima (20 mg t-PA) and Seattle (24 mg t-PA) studies.In contrast to the ULTIMA and Seattle study protocols, the current study used EKOS fibrinolysis delivery catheter as a diagnostic tool to measure the pulmonary artery pressure invasively before and 6 h after the initiation of the procedure. The results matched the right heart catheter results in the EKOS and Heparin arm in the Ultima trial, thereby confirming the validity of this diagnostic tool to assess therapy effectiveness and to identify PE with risk of adverse outcomes.The apparent reduction related complications of additional procedures, hospital residency, and economics gives this therapy additional diagnostic potential. Further, it stresses the importance of an interdisciplinary team in the management of PE.On 21 May 2014, based on the data from Ultima, Seattle II, and PEITHO trials along with previous studies, the U.S. Food and Drug Administration approved the Eko-Sonic Endovascular System for the treatment of PE ,15. We tThe current ESC guidelines  recommenOur study expands the experience of ultrasound-facilitated and catheter-directed low-dose fibrinolysis in patients with intermediate–high and high-risk PE and demonstrates the potential of this technique, even in high-risk PE patients with moderate risk of bleeding. In the overall safe population, neither ICH nor the recurrency of PE was observed. Deaths were observed for two patients early after therapy  as well as three patients by 90 days .This study demonstrated that a lower dose and short duration of t-PA treatment was associated with significant improvements in hemodynamics and few major bleeding events. Our study took into consideration the quality of life within 90 days using the German EQ-5D-3L questionnaire. The OPTALYSE-PE trial demonstrated an improvement in functional performance, 6MWT, and quality of life from the interval of 1 month to 1 year after initial therapy . FinallyThe major limitation of this study was the lack of a control group. Therefore, we cannot comment on the effectiveness and safety of fibrinolysis using a delivery catheter as a diagnostic tool to evaluate hemodynamics compared with anticoagulation alone or with other interventional modalities. However, the Ultima trial reported significant improvements in hemodynamics using right heart catheterization, CT, and an echocardiographic parameter in the USCDT and Heparin group, unlike the anticoagulation one.Another potential treatment is catheter-directed low-dose fibrinolysis therapy without the use of ultrasound to investigate and understand the impact of ultrasound facilitation, especially in chronic intermediate PE or in cancer patients, where the thrombus is more organized and fibrotic than in acute PE.An important limitation was the lack of a right heart catheter in follow-up for estimation of pulmonary artery systolic pressure within 90 days, as was the lack of a randomized design to minimize bias.The population was racially and ethnically homogenous as a solely Caucasian population, with no other groups present.In summary, this protocol used a lower dose and shorter duration of t-PA in 45 PE patients, demonstrating similar safety and effectiveness outcomes. It focused on pulmonary artery hemodynamic as a primary precise surrogate marker for therapy effectiveness assessed by fibrinolysis delivery catheter. It confirmed the validity of this diagnostic tool and stressed the importance of an interdisciplinary team in the management of PE. Ultrasound-facilitated catheter-directed low-dose fibrinolysis does not result in intracranial hemorrhage, reduces pulmonary artery pressure, decreases the RV/LV diameter ratio, improves the RV function, relieves symptoms in acute intermediate high-risk PE, and improves quality of life. In addition to these therapeutic benefits, an EKOS fibrinolysis delivery catheter can be used as a valid diagnostic tool to assess therapy effectiveness by measuring pulmonary artery hemodynamics. Lower doses and short duration of therapy could further reduce the complication with similar efficacy outcome, thus improve health, economics outcomes and shortens ICU stay. This study demonstrated that ultrasound-facilitated catheter-directed fibrinolysis for the treatment of 45 patients with intermediate- to high-risk pulmonary embolism was associated with significant improvements in hemodynamics and few major bleeding events, as demonstrated in previous trials (Ultima and Seattle II). However, this protocol used lower doses and a shorter duration of t-PA treatment, which shortens ICU stay to 6 h.This study focuses on pulmonary artery hemodynamic measured by a fibrinolysis delivery catheter as a primary precise surrogate marker to ensure effectiveness, in addition to the RV/LV ratio that was used in previous trials (Ultima and Seattle II), which has a bias of interobserver variability.This is a valid and precise diagnostic tool that can be used to assess therapy effectiveness and identify PE cases at risk of adverse outcomes such as chronic thromboembolic pulmonary hypertension (CTEPH), which may cause significant morbidities, as well as reduce the related complications of additional procedures, hospital residency, and economics. This gives this therapy potential as an additional diagnostic.Our results stress the importance of an interdisciplinary team in management of PE, and the study evaluated the quality of life of the patients. This protocol shortens ICU stay to 6 h.Although ultrasounds separate fibrin strands, enhancing the penetration of the thrombolytic agent into the emboli through low-dose fibrinolysis applied locally to reduce the bleeding complication, reduce the dose of administration, and at the same time achieve a reduction in the pulmonary artery pressure, it is paramount to assess the efficacy and safety outcomes of this therapy with other interventional modalities in order to better understand the optimal use of this therapy for acute PE.Ultrasound-guided puncture should be assessed to identify whether this tool influences major and minor adverse outcomes in PE or not.Pulmonary artery hemodynamic assessments using the EkoSonic Endovascular System fibrinolysis delivery catheter should be evaluated in a randomized trial investigating whether the treatment of high-risk PE favorably influences major adverse outcomes compared to standard therapy . A HI-PEITHO study is underway .


All epicardial procedures under general anesthesia with one-lung ventilation were successfully completed in 1.0 ± 0.4 h without phrenic nerve stimulation. LV pacing thresholds in the epicardial-LV (1.5 ± 1.0 V) and endocardial-LV (1.3 ± 0.8 V) were comparable (p = 0.651). All patients were discharged alive post-VATS 8.8 ± 3.9 days. During the follow-up (34.3 ± 28.6 months), all patients with epicardial LV leads stayed alive except for one cardiac death post-CRT 14 months and one heart transplantation post-CRT 30 months. All epicardial LV leads maintained stable performance without dislodgement/significant changes in pacing threshold/impedance. LV lead dislodgement occurred only in endocardial-LV . Efficacy in both groups was comparable in terms of QRS narrowing, increase in LV ejection fraction, and survival free of cardiac death, or heart-failure-related hospitalization. (4) Conclusions: Epicardial LV lead placement using VATS can be a safe and effective alternative to endocardial implantation, with comparable acute and post-discharge outcomes achieved by both approaches.(1) Background: Limited data exist on the safety and efficacy of epicardial left ventricular (LV) lead placement using video-assisted thoracoscopic surgery (VATS) for cardiac resynchronization therapy (CRT). (2) Methods: Acute and post-discharge outcomes of CRT were compared between patients with epicardial LV leads (Epicardial-LV group,  Cardiac resynchronization therapy (CRT) in the form of biventricular stimulation decreases mortality and morbidity in selected patients with symptomatic heart failure (HF) characterized by interventricular conduction delay ,2,3,4,5.In our center, a minimally invasive video-assisted thoracoscopic surgery (VATS) began to be actively utilized in March 2010 for epicardial ablation of atrial fibrillation or implantation of LV leads, avoiding more invasive median sternotomy or full thoracotomy ,11,12. IFrom October 2005, we prospectively entered information into our registry of cardiac implantable electronic devices on demographic, clinical, and device-related parameters in conjunction with electrocardiographic and echocardiographic data for all patients undergoing CRT implantation at our institution. In the registry, we carefully searched for consecutive patients with epicardial LV lead placement . As a control group, data on consecutive patients who received successful transvenous LV lead placement during the same study period were also obtained . Exclusion criteria were (1) replacement of CRT device, (2) epicardial LV implantation during open chest surgery, (3) in-hospital death, and (4) loss to follow-up after CRT implantation . All patEpicardial LV lead implantation using VATS was performed as a second stage procedure after RV and RA leads were implanted in the electrophysiology laboratory. Under general anesthesia, using double endoluminal intubation for selective lung ventilation, patients were placed in the right lateral decubitus position with the left chest elevated 30–40°. The left subclavian generator pocket created during the previous endocardial approach was reopened before one-lung ventilation. A 2 cm incision for a 15 mm port was made in the sixth left intercostal space at the posterior axillary line. A 30° thoracoscope was inserted through the 15 mm port for inspection of the left thoracic cavity. Two additional 5 mm ports were positioned in the fourth left intercostal space anterior to the anterior axillary line for the second port and mid-axillary level for the third port for introducing thoracoscopic grasp and dissector, respectively a. In casTo assess in-hospital outcomes in the Epicardial group, we evaluated procedure time, the success rate of implantation, immediate QRS narrowing, any change in NYHA functional class, post-implant duration of care at intensive care unit (ICU), length of post-implant hospital stay, mortality, and procedure-related complications .p%) reports were obtained at each clinic visit. The BiV-p% was calculated by averaging the values obtained at 3 months, 12 months, and the last visit after the procedures. During the follow-up period, adjustments to CRT pacing parameters such as pacing rate, mode, and atrioventricular/ventriculoventricular delay were left to the physician’s discretion.After discharge, clinical follow-ups with CRT-device interrogations were performed approximately 2 weeks after surgery and then every 3 months or when clinically indicated at our dedicated device clinic. Chest X-ray, 12-lead electrocardiograms, and biventricular pacing percentage  were compared between the Epicardial and Endocardial groups. Pre- and post-operative assessments of LVEF, LV end-diastolic volume (EDV), and LV end-systolic volume (ESV) were obtained using commercially available equipment . All death cases were defined as cardiac origin unless a definite non-cardiac cause could be identified. HF hospitalization was confirmed according to the 2016 European Society of Cardiology guidelines following careful assessment of HF symptoms or signs, chest radiography, echocardiography, and biomarkers.t-test when appropriate. Continuous variables between the Epicardial and Endocardial groups were compared using the Mann–Whitney test. Relative change in QRS duration (QRSd), LV volumes, and LV lead pacing variables were calculated as the differences between the last follow-up values and the baseline values divided by the baseline values. The probability of freedom from events was calculated according to the Kaplan–Meier method. A p-value < 0.05 was considered to indicate statistical significance. All statistical analyses were performed using SPSS version 25.0 .Baseline data are presented as frequencies or the mean ± standard deviation (SD). Categorical variables were compared using χ2 tests. Comparisons of continuous variables in the same patients were performed using Wilcoxon signed-rank test or paired n = 5), tortuous coronary sinus and/or target branches (n = 3), anomalous cardiac veins (n = 3), or recurrent dislodgement of previous LV lead (n = 2). The mean (±SD) age of the 13 patients was 61.9 ± 8.9 years, and male patients accounted for 46% (n = 2), valve replacement (n = 2), CABG with valve replacement (n = 1), and closure of ventricular septal defect (n = 1).From December 2011 to September 2020, we identified 13 consecutive patients who underwent VATS epicardial LV lead implantation after the failure of the percutaneous approach due to the absence of suitable lateral cardiac vein ( for 46% . An NYHAp = 0.019) and more frequent previous cardiac surgery  in the Epicardial group  or along with mini-thoracotomy (n = 5) without significant immediate post-procedural complications. Mini-thoracotomy was needed in five patients with pleural adhesions. Of the five patients, three had a previous cardiac surgery such as CABG or ventricular septal defect closure. General anesthesia with one-lung ventilation was well tolerated by all patients. The mean (±SD) procedure time was 1.0 ± 0.4 h. The immediate post-implant LV pacing threshold was 1.5 ± 1.0 V (at 0.5 ± 0.1 ms of pulse width), which was not significantly different from that of the Endocardial group  (p = 0.001). There was no PNS, hemothorax, or lead dislodgement during the index hospitalization.All epicardial implantations of LV leads were successfully completed via VATS alone (= 0.651) . All patPost-discharge performance of epicardial LV leads was evaluated and compared with that of endocardial LV leads (p = 0.154) and impedance  during the 34.3 ± 28.6 months of follow-up (LV leads . The Epiollow-up . In addiollow-up . In the p = 0.023), while it increased from 25.6 ± 6.2% to 38.1 ± 14.5% in the Endocardial LV group (p < 0.001).The efficacy of CRT with epicardial versus endocardial leads was also compared during the post-discharge 34.3 ± 28.6 months of follow-up. Patients in the two groups revealed a marked and comparable QRS narrowing. Additionally, a remarkable LV reverse remodeling was observed in terms of LVEF increase and LVESV reduction. The LVEF increased from 25.7 ± 3.9% to 37.7 ± 15.1% in the Epicardial LV group (p = 0.544), cardiac death including left ventricular assist device implant and heart transplantation (p = 0.749), and HF hospitalization (p = 0.700) were comparable between the two groups  outcomes with regard to LV lead performance, electro-/echocardiographic improvement, and clinical prognosis of patients, compared with those using a conventional endocardial approach. Our results are in line with data from Marini et al., who demonstrated no differences in death, cardiovascular hospitalizations, or device-related complications between the Epicardial  and Endocardial groups during a median follow-up of 24 months .Appropriate LV lead placement into the optimal pacing site is important for the correction of LV dyssynchrony and leads to better clinical outcomes of CRT ,21,22. EThere are several concerns about the implantation of epicardial LV leads using VATS. First, many physicians may be reluctant to refer patients for this surgical treatment because general anesthesia with one-lung ventilation itself can aggravate patients with severe LV systolic dysfunction. Second, extensive experience of operators is required for this thoracoscopic technique. Finally, if the VATS approach fails, total operation time may be more prolonged with median sternotomy or left thoracotomy eventually required. However, general anesthesia with one-lung ventilation was well tolerated by all of our patients with severe LV systolic dysfunction . Additionally, pacing threshold and impedance were found to be stable and within a clinically acceptable range over the entire follow-up period in the VATS epicardial LV lead group. Ceresa et al. also found that the screw-in of the epicardial LV lead through a small mini-thoracotomy ensures a low pacing threshold and stable impedance both in early and medium terms, supporting our results . No signOne of the major limitations of this study is the retrospective, observational design of the analysis. Second, small numbers of patients in the single-center in the Epicardial LV lead group may produce bias; thus, prospective randomized studies on a larger scale are needed to validate the efficacy and safety of the LV lead implant using VATS for CRT more definitely. Finally, only screw-in unipolar pacing leads were used in this study. Therefore, current results cannot be generalized and compared with bipolar systems. However, Ceresa et al. have already shown the stable and satisfactory performance of bipolar pacing leads in their own data .Where suitably trained thoracoscopic surgeons are available, epicardial LV lead implantation using VATS can be an effective and safe alternative to the standard transvenous approach in CRT patients with difficult vein anatomy or endocardial lead dislodgement. The VATS epicardial LV leads implantation showed stable acute and post-discharge performance, offering comparable CRT outcomes to those observed in patients treated using endocardial LV leads.


Diastolic dysfunction often complicates myocardial ischemia with increased mortality rates. However, less is known about diastolic function after perinatal asphyxia in neonates with hypoxic-ischemic encephalopathy (HIE) during therapeutic hypothermia (TH) and rewarming.The aim of this study was to assess diastolic function with tissue Doppler imaging (TDI) in neonates with moderate–severe HIE during TH and rewarming.Newborns at >36 weeks' gestation with moderate–severe HIE treated with TH were evaluated with targeted neonatal echocardiography (TNE), including TDI, within 24 h of TH initiation (T1), at 48–72 h of treatment (T2), and after rewarming (T3). These retrospective data were collected and compared with a control group of healthy babies at >36 weeks' gestation that was prospectively evaluated following the same protocol.A total of 21 patients with HIE + TH and 15 controls were included in the study. Myocardial relaxation before the onset of biventricular filling was prolonged in the HIE + TH group during TH with significantly longer isovolumic relaxation time (IVRT') in the left ventricle (LV), the septum, and the right ventricle (RV). This was associated with slower RV early diastolic velocity (e') and prolonged filling on T1. Total isovolumic time  and myocardial performance index (MPI') were globally increased in asphyxiated neonates. All these differences persisted after correction for heart rate (HR) and normalized after rewarming. TDI parameters assessing late diastole (a' velocity or e'/a' and E/e' ratios) did not differ between groups.TDI evaluation in our study demonstrated a pattern of early diastolic dysfunction during TH that normalized after rewarming, whereas late diastole seemed to be preserved. Our data also suggest a possible involvement of impaired twist/untwist motion and dyssynchrony. More studies are needed to investigate the impact and therapeutic implication of diastolic dysfunction in these babies, as well as to clarify the role of TH in these findings. Cardiovascular impairment is a frequent complication among neonates with hypoxic-ischemic encephalopathy (HIE) and has been associated with a worse neurodevelopmental outcome. Myocardial dysfunction in the context of altered cerebral blood flow autoregulation may delay brain reoxygenation after hypoxia-ischemia and consequently aggravate injury . HemodynIn this regard, most studies have focused on the impact of perinatal hypoxia-ischemia on the systolic function of the left ventricle (LV). Only recently, the predominant vulnerability of the right ventricle (RV), and more importantly, the association of RV dysfunction with adverse neurologic outcomes, has been suggested , 3. SurpDiastole is a key component of heart function as adequate relaxation and ventricular filling are necessary for a normal systolic performance . EvaluatThe aim of this study was to assess diastolic function with TDI in newborns with moderate–severe HIE during TH and rewarming, with the hypothesis that diastolic dysfunction is another consequence of myocardial damage after HIE.We conducted a retrospective study on newborns with moderate–severe HIE treated with TH at a tertiary neonatal intensive care unit (NICU).All patients with HIE treated with TH (HIE + TH group) admitted to the NICU at Hospital Clínico San Carlos between October 2017 and October 2019, with echocardiographic evaluations, including TDI, were eligible for enrollment. Diagnosis of congenital heart disease, decision not to provide full life support on admission, or lack of TDI assessment were considered exclusion criteria .Their data were compared with a prospectively recruited control (CTL) group of healthy neonates .The study was approved by the local Ethics Committee. An exemption of formal consent was obtained for the inclusion of retrospective data. Parental informed consent was obtained before the enrollment of control babies.We collected relevant demographic and clinical data of patients and controls. Gestational age, birth weight, gender, Apgar scores, cord pH, modified Sarnat score, and respiratory and cardiovascular support were recorded.The neonatal echocardiography (TNE) evaluations were performed according to our NICU protocol within 24 h of TH initiation (T1), at 48–72 h of treatment (T2), and after rewarming (T3), and at equivalent time points in the CTL group, by three different operators . These studies were performed as part of the routine care of these babies to guide treatment. The use of inotropes was indicated by the attending team based on ultrasound or on clinical parameters. Images were recorded and stored in digital format for offline analysis by a single investigator (MJR). Studies were performed using a portable ultrasound device  with a 12-MHz transducer probe. Standard transthoracic two-dimensional, M-mode, pulsed-wave (PW) Doppler, and PW TDI images were obtained for analysis.Conventional echocardiographic measurements were performed according to published guidelines refer to  and averThe primary outcomes of the study were TDI myocardial diastolic velocities and time intervals. PW TDI was performed by adjusting the spectral pulsed Doppler signal filters to obtain a Nyquist limit of 15–20 cm/s and using the minimal optimal gain according to the published guidelines . TDI velTime intervals were corrected to the heart rate (HR) as calculated with the RR interval and reported as ET'/HR, IVCT'/HR, IVRT'/HR, FT'/HR, and t-IVT'/HR.2 of 3.8, the calculated sample size was 16. The final number of babies in the control group was 15, because data from one of the babies had to be eliminated. All babies from the study group were included in the analysis. Comparison between HIE + TH and control groups was analyzed using generalized estimating equation (GEE) models with an exchangeable correlation structure. The cardiac variables were introduced in each model as dependent variables and the treatment group (TH vs. control), different time points, and the interaction term between group and time points as independent variables. The results are presented as the means and 95% confidence intervals obtained through the margins postestimation STATA command after fitting each model. The means of intragroup comparison between the treatment group (TH vs. control) in each time point and the intragroup differences, taking the time point one as reference, were made using the Bonferroni method for multiple comparisons. A value of p < 0.05 was accepted for statistical significance. The STATA version 15.0. software was used for the statistical analysis.Considering the results of diastolic myocardial velocity measurements, for a statistic power of 90%, 1-α of 95% with d = −2, and SA total of 21 patients with HIE + TH (five girls and 16 boys) were consecutively included in the study as well as 15 controls (five girls and 10 boys) . Tables The results of conventional echocardiographic measurements are described in the Electronic TDI results are summarized in Left ventricular (LV) myocardial systolic velocities were similar in both groups at all time points. In contrast, septal s' was decreased in patients with HIE + HT in T1 compared to controls and increased significantly after rewarming. RV s' did not differ from controls at any time point but it increased significantly in asphyxiated babies after rewarming.LV) and late (a'LV) diastolic velocities, as well as E/e'LV and e'/a'LV ratios. Septal a' was significantly slower at T2 in asphyxiated neonates and increased significantly after rewarming, but e'SEPTAL and e'/a'SEPTAL did not differ between groups or time points. Regarding RV diastolic velocities, e' was significantly slower at the first assessment in the HIE + TH group and improved after rewarming. However, no differences were found for a'RV, E/e'RV, or e'/a'RV between groups and time points except for a significant increase in a'RV and e'/ a'RV after rewarming compared to baseline values in patients with HIE.The LV diastolic myocardial velocities were similar in both groups, without differences for early  was significantly longer in LV, septum, and RV in babies with HIE during TH compared to controls, with a significant decrease in T2 and after rewarming.In this retrospective study, we demonstrated the existence of a significant diastolic dysfunction in cooled neonates with moderate–severe HIE that improves progressively during treatment and normalizes after rewarming. TDI evaluation in our study showed a pattern of early diastolic dysfunction during TH, whereas late diastole seemed to be preserved.This is one of the first studies specifically assessing biventricular diastolic function using TDI during TH and rewarming. We observed an increase in MPI' in both ventricles and the septum during TH that normalized after rewarming. Increased MPI is one of the most consistent echocardiographic findings in studies on HIE and reflects an alteration of combined systolic and diastolic function –19. In tDiastole can be divided into two different phases, namely, early and late diastole. The complex distribution and orientation of the different myocardial muscle layers are key anatomic factors that explain not only the highly efficient pumping of blood during systole but also the mechanisms of ventricular filling in early diastole. During IVRT, the clockwise relaxation of the transverse myocardial band and the cessation of contraction of the inner descending fibers, together with the contraction of the outer ascending layer, generate the powerful suction force that is critical for the rapid early filling of the LV after mitral valve opening . We founper se can induce diastolic dysfunction (Rapid early ventricular filling is followed by a transient decrease in flow (diastasis) after which atrial contraction collaborates to a further increase in ventricular filling during the late phase of diastole. Traditionally, relaxation parameters are used to characterize early diastole, whereas compliance and filling pressure parameters are used to characterize late diastole . Slow refunction , 38. Howfunction , 20.Prolongation of isovolumic relaxation can also be the result of alternative mechanisms, such as altered twist/untwist motion or intraventricular dyssynchrony, both of which impact early diastolic suction . In thisOur study has some limitations. First, most patients were receiving dobutamine during the echocardiographic assessments and this could have influenced our results. In this regard, some studies have reported an improvement in diastolic function with this treatment . Thus, tIn conclusion, our study demonstrates the presence of diastolic dysfunction in neonatal HIE during TH characterized by globally prolonged IVRT' and decreased early diastolic RV myocardial velocity, regardless of HR, which normalized after rewarming, reflecting a prolonged and slowed myocardial relaxation. We also found data, suggesting an altered myocardial twist/untwist motion and ventricular dyssynchrony. Diastolic impairment may not be clinically evident in the setting of hypothermia-induced bradycardia, so echocardiographic assessment of myocardial function during TH should include the evaluation of diastolic function with appropriate techniques, such as TDI. Further studies are needed to investigate the impact of diastolic dysfunction on HIE as well as its potential therapeutic implications.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics Committee in Clinical Research, Hospital Clinico San Carlos, Madrid, Spain. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.LA and MJR: study design. MJR, AC, and LA: acquisition of data. JM-O and IS: data analysis. MJR, JM-O, IS, and LA: interpretation of data. MJR, LA, and JM-O: manuscript drafting. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


As automated echocardiographic analysis is increasingly utilized, continued evaluation within hospital settings is important to further understand its potential value. The importance of cardiac involvement in patients hospitalized with COVID-19 provides an opportunity to evaluate the feasibility and clinical relevance of automated analysis applied to limited echocardiograms.In this multisite US cohort, the feasibility of automated AI analysis was evaluated on 558 limited echocardiograms in patients hospitalized with COVID-19. Reliability of automated assessment of left ventricular (LV) volumes, ejection fraction (EF), and LV longitudinal strain (LS) was assessed against clinically obtained measures and echocardiographic findings. Automated measures were evaluated against patient outcomes using ROC analysis, survival modeling, and logistic regression for the outcomes of 30-day mortality and in-hospital sequelae.Feasibility of automated analysis for both LVEF and LS was 87.5% (488/558 patients). AI analysis was performed with biplane method in 300 (61.5%) and single plane apical 4- or 2-chamber analysis in 136 (27.9%) and 52 (10.7%) studies, respectively. Clinical LVEF was assessed using visual estimation in 192 (39.3%), biplane in 163 (33.4%), and single plane or linear methods in 104 (21.2%) of the 488 studies; 29 (5.9%) studies did not have clinically reported LVEF. LV LS was clinically reported in 80 (16.4%). Consistency between automated and clinical values demonstrated Pearson's R, root mean square error (RMSE) and intraclass correlation coefficient (ICC) of 0.61, 11.3% and 0.72, respectively, for LVEF; 0.73, 3.9% and 0.74, respectively for LS; 0.76, 24.4ml and 0.87, respectively, for end-diastolic volume; and 0.82, 12.8 ml, and 0.91, respectively, for end-systolic volume. Abnormal automated measures of LVEF and LS were associated with LV wall motion abnormalities, left atrial enlargement, and right ventricular dysfunction. Automated analysis was associated with outcomes, including survival.Automated analysis was highly feasible on limited echocardiograms using abbreviated protocols, consistent with equivalent clinically obtained metrics, and associated with echocardiographic abnormalities and patient outcomes. The use of artificial intelligence (AI) as a method for automating medical image analysis has the potential to transform patient care . In echoContinued assessment of automated analysis using real-world data is essential to evaluate potential feasibility and relevance to clinical practice. In cases of severe infection, coronavirus disease 2019 (COVID-19) patients frequently present with prognostically significant cardiac involvement . EchocarIn this multi-site, retrospective study, we sought to evaluate (1) the feasibility of automated quantification of LV systolic function using limited echocardiograms from COVID-19 patients; (2) the agreement between automated quantification and clinical findings; (3) the association of automated assessment of the LV with in-hospital patient outcomes.This study was approved by the Institutional Review Boards and conducted among consecutive inpatient adults diagnosed with COVID-19 (positive antigen or polymerase chain reaction test) who underwent clinically indicated transthoracic echocardiography at six institutions: Beth Israel Deaconess Medical Center, Harvard Medical School (Boston); Temple University Hospital (Philadelphia); Einstein Medical Center (Philadelphia); Ochsner Medical Center (New Orleans); The University of Pittsburgh Medical Center; and Mayo Clinic Health System sites across Minnesota, Wisconsin, Florida, and Arizona, between February and December 2020. Only the first transthoracic echocardiogram performed during the hospital admission for COVID-19 was considered. Echocardiographic studies were included in the analysis if either an apical 4-chamber or apical 2-chamber image clip was available for analysis. Those with insufficient image quality to assess LV ejection fraction (EF) clinically and to evaluate the AI derived contours of the LV were excluded.Patient baseline characteristics, medical history, and in-hospital outcomes were obtained at each site from review of electronic health records. These included patient demographics, presenting signs/symptoms, comorbidities at the time of initial hospital presentation, in-hospital sequelae, and echocardiographic findings. Outcomes included 30-day all-cause mortality, incident acute coronary syndrome (ACS), congestive heart failure (CHF), acute kidney injury, and major adverse cardiovascular and cerebrovascular events (MACCE), defined as the composite of ACS, CHF, stroke, coagulation disorder (disseminated intravascular coagulation or other acquired bleeding disorder), myocarditis, or pericarditis. Coronary artery disease (CAD) was defined as prior myocardial infarction (MI), coronary revascularization, or angiography showing stenosis >50% diameter. Echocardiographic variables were obtained from echocardiography reports and included (where available) qualitative assessment of cardiac function .As echocardiographic data was collected predominantly during the first wave of the pandemic, abbreviated and focused protocols were frequently utilized to minimize scan times and staff exposure risk , sometimQuantitative assessment of LV function was obtained from clinical echocardiographic reports. The method of LVEF quantification  was recorded. Protocols for echocardiographic acquisition and quantification were conducted according to local procedures and clinical standards in place at the time of data collection.Quantitative assessment of LV function was obtained from automated AI driven echocardiography analysis algorithms . LV LS was calculated as the average of the end-systolic longitudinal strain from apical 4- and 2-chamber views. Where one view was unavailable, single view longitudinal strain values were calculated. LV volumes and LVEF were determined using the Simpson's biplane method of disks. Where biplane LVEF was not feasible with both apical 4- and 2-chamber views, a single plane LVEF was calculated when feasible. The AI algorithms process apical 4- and 2-chamber images to automatically select cardiac cycles, contour the endocardial border, and calculate volumes, ejection fraction and longitudinal strain . Data foThe endocardial border of apical 4- and 2-chamber images were automatically contoured by EchoGo Core and were presented to operators for approval. All operators held professional qualifications in echocardiography . All studies were processed through EchoGo Core, irrespective of image quality. A study was considered feasible for AI analysis if operators approved either apical 4- or 2-chamber views. Studies where AI analysis was not feasible  were included in the feasibility evaluation but not in the final analysis.t-test or the Wilcoxon rank sum test, as appropriate. Categorical data was presented as counts and percentages and compared using the χ2 test. Pairwise comparisons of continuous and categorical data were conducted using paired t-tests and McNemar's test, respectively. Agreement analysis was conducted using Bland Altman statistics, linear Deming regression root mean square errors (RMSE), Pearson's correlation coefficients, and intraclass correlation coefficients (ICC). For agreement of LVEF between AI and clinical values, the analysis was conducted using comparable methods . Discordance between automated and clinically assessed LVEF was defined by an inter-method difference of >10%, which has been reported as the minimum detectable difference between observers  or medians and interquartile ranges (IQR). Continuous data were compared between groups based on automated LS and EF using the Student's bservers , 34. Forbservers , 35, 36.bservers , 35, 36.bservers  with potbservers , 38. AllOf 558 patient echocardiograms with at least one apical cardiac cycle, automated analysis of both LVEF and LS was feasible in 488 (87.5%). AI feasibility was 93.7% for the Mayo Clinic, 80.8% for Beth Israel Deaconess Medical Center, 100% for the University of Pittsburgh, 91.5% for Ochsner Medical Center, 72% for Temple University Medical Center and 89.7% for Einstein Medical Center . ReasonsOf the 488 accepted studies, AI analysis was performed with biplane method in 300 (61.5%) and single plane apical 4- or 2-chamber analysis in 136 (27.9%) and 52 (10.7%) studies, respectively. Clinical assessment of LVEF was recorded in 459 (94.1%) of the 488 studies at the time of the echocardiogram. Clinical LVEF was assessed using visual estimation in 192 (39.3%), biplane methods in 163 (33.4%), and single plane or linear methods in 104 (21.2%). LV LS was clinically reported in 80 (16.4%) patients.Baseline patient characteristics, demographics, and clinically derived echocardiographic parameters are reported in Comparison of the AI derived assessment to the values obtained from clinical echocardiography reports is reported in The relationship of AI derived assessment and reported echocardiographic abnormalities was examined . AI derip = 0.11) or LS . Automated and clinical assessment of LS and LVEF demonstrated inter-method agreement in 70.0 and 79.6% of cases, respectively, when identifying LVEF <50% or LS >–16%, respectively. For LVEF, there were 61 (13.3%) cases where the automated assessment was <50% but the clinical values were >50% and 33 (7.2%) cases where the automated assessment was >50% and the clinical assessment was <50%. AI reported LVEF was different by a margin of more than 10% in 164 patients (36%) with 73% of these occurring in patients where the clinical assessment was performed using linear or manual methods. For LS, there were 11 (13.8%) of 80 cases where the automated assessment was >–16% and the clinical assessment was < –16% and 13 (16.3%) cases where the automated assessment was <–16% but the clinical assessment was >–16%. When comparing patients identified by clinically derived LVEF and LS, automated assessment characterized a significantly smaller proportion as abnormal [AI vs. clinical: LVEF: 56 (12.2%) patients vs. 89 (19.3%) patients, p < 0.001, LS: 18 (22.5%) patients vs. 31 (38.8%) patients, p < 0.001, ROC analysis of the ability of AI LVEF and LS to identify clinical systolic dysfunction  achieved an area under the curve of 0.894 and 0.863, a sensitivity of 85.7% and 81.3%, and a specificity of 78.6% and 83.1%, respectively . Pairwisp = 0.025, LS p = 0.03), ACS , CHF , acute kidney injury , and MACCE during hospital admission . Automated LVEF and LS were associated with mortality using Cox regression to account for increased risk over longer durations of hospitalization  and MACCE,  but not in-hospital death  or acute kidney injury . Clinical LVEF (p < 0.001) but not LS (p =0.118) was associated with ACS. Cox regression of clinical LVEF and LS was associated with mortality for LVEF (p = 0.019) but not for LS , acute coronary syndrome in 39 (8%), congestive heart failure in 49 (10%), and MACCE in 117 (24.0%). Using logistic regression adjusted by site , automatp > 0.05). Kaplan Meier analysis demonstrated increased risk of death for those with abnormal LVEF, relative to normal LVEF, for both clinical (log-rank p = 0.004) and automated (log-rank p = 0.01) assessment. Relative to borderline LVEF, patients with abnormal LVEF demonstrated increased likelihood of death for clinical assessment (log-rank p = 0.01) but not for automated assessment (log-rank p = 0.19).When categorized into hyperdynamic, normal, borderline, and abnormal classes based on LVEF, survival rates were 77.6, 83.3, 85.1, and 71.1%, respectively, for clinical LVEF and 81.7, 84.8, 80.0, and 71.6%, respectively, for automated LVEF . When caThis study has evaluated the feasibility and clinical relevance of automated echocardiographic analysis software on a multi-site COVID-19 cohort, with an ethnically diverse population (50% non-Hispanic white), using limited echocardiographic studies. The main findings are: (1) Automated analysis of limited echocardiograms was feasible in 87.5% of patients in which at least one apical cardiac cycle was obtained, even under abbreviated protocols, with biplane analysis of LVEF and LS possible in 61.5% of patients; (2) Automated LVEF, LS, and volumes had good to excellent agreement with clinically derived values; (3) Automated LVEF and LS were able to stratify individuals with cardiac dysfunction, including clinically reported echocardiographic abnormalities; (4) Automated LVEF and LS were associated with adverse in-hospital and 30-day outcomes and were comparable to clinically derived assessment. These findings suggest that automated assessment of LV function is highly feasible under abbreviated protocols and provides prognostically relevant information while increasing the data available for risk stratification.During the COVID-19 pandemic, it was quickly reported that cardiac complications were common in cases of serious infection and were associated with poor patient outcomes –41. WhilIn addition to high feasibility, the ability to provide clinically relevant information to assist in patient risk stratification is a core requirement for medical devices. In the present study, patients with an automated LS of >–16% or LVEF of <50% were more likely to present with clinically identified cardiac abnormalities such as LV hypertrophy, regional wall motion abnormalities, and left atrial enlargement. Furthermore, both LS and LVEF were significantly associated with poor patient outcomes, with LS identifying patients with a 29% increased risk of MACCE  per 1% increase (less negative) in LS. The risk of adverse in-hospital outcomes when stratified by LVEF or LS was largely consistent between clinical and automated assessments, providing further evidence of the validity of automated analysis. These findings are in line with recent work reporting that abnormal systolic LV function, as defined by AI derived LVEF and/or LS, are associated with adverse cardiac events and death , 18. ImpTechnological advances in both computing and instrumentation have steadily increased the availability of quantitative echocardiographic assessment in routine practice. Such assessment, including LS, have consistently demonstrated value for patient risk stratification and prognostication in a range of conditions –47. HoweAn important finding of this study was the discordance between automated and clinical characterization of abnormal systolic function by LVEF and LS. Automated and clinical assessment were discordant in 20 and 30% of cases for LVEF and LS, respectively. When comparing those deemed to have abnormal LVEF and LS using clinical assessment as the reference, classifications using automated assessment identified a significantly smaller population as abnormal . However, this investigation did not demonstrate significant differences in relationship to overall mortality when stratified using clinical or automated assessment; thus, the clinical implications of such discrepancies are unclear. Such differences may reflect a bias from clinical interpretation of echocardiograms, where additional information can support differential diagnosis while the use of only apical views for automated assessment may underestimate patient risk. Indeed, the use of limited methods in the clinical estimation of LVEF  contributed to 73% of the observed differences of more than 10% between AI and the clinical interpretation. Although no differences were observed in patient outcomes between AI and clinical methods, limited sample size and a relatively low event rate precluded further investigation of the clinical implications of discordance between the AI and the clinical interpretation. Further work is required to understand the relationship between automated assessment and clinical interpretation for risk stratification.This study has several limitations. The retrospective nature of the investigation limits the generalizability of the findings to routine practice and further work is required to understand the real-time implications of the AI technology in varied populations. In addition, the clinical assessment of LVEF or LS was limited and as such, a comparison of AI feasibility to clinical feasibility was not possible. The limited sample of clinical LS values is a significant limitation when evaluating the association with patient outcomes. Automated assessment of RV function was not conducted and may have provided further prognostic information , 37. SecIn a multi-center study conducted during a pandemic, automated analysis of ultrasound images was highly feasible, correlated with clinical observation, and associated with outcome.The anonymized and aggregate raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Mayo Clinic Institutional Review Board. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.PP, WH, and GW designed the study. PP and WH drafted the manuscript. CS and WH organized the database and performed statistical analysis. JS and GP-H obtained local approval and data collection for Beth Israel Deaconess Medical Center. MK and BK obtained local approval and data collection for Temple Heart and Vascular Center. SQ and AT obtained local approval and data collection for Ochsner Health System. FG and EP obtained local approval and data collection for Einstein Medical Center. RT and SW obtained local approval and data collection for University of Pittsburgh. DM and TN obtained local approval and data collection for Mayo Clinic Scottsdale Arizona. PP oversaw local approval and data collection for Mayo Clinic Rochester Minnesota. All authors contributed to manuscript revision and read and approved the submitted version.GW and WH are employed by Ultromics Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. This study received funding from Ultromics Ltd. The funder had the following involvement with the study: The AI measurements in this study were performed by Ultromics Ltd.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Left bundle branch block (LBBB) is a ventricular conduction delay with high prevalence. Aim of our study is to identify possible recurring patterns of artefacts in late gadolinium enhancement (LGE) imaging in patients with LBBB who undergo cardiac magnetic resonance imaging (MRI) and to define parameters of mechanical dyssynchrony associated with artefacts in LGE images.Fifty-five patients with LBBB and 62 controls were retrospectively included. Inversion time (TI) scout and LGE images were reviewed for artefacts. Dyssynchrony was identified using cardiac MRI by determining left ventricular systolic dyssynchrony indices  derived from strain analysis and features of mechanical dyssynchrony .p < 0.05 with an area under the curve of 0.863 . Septal flash and apical rocking were more frequent in the LBBB with artefact group than in the LBBB without artefact group .Thirty-seven patients (67%) with LBBB exhibited inhomogeneous myocardial nulling in TI scout images. Among them 25 (68%) patients also showed recurring artefact patterns in the septum or free wall on LGE images and artefacts also persisted in 18 (72%) of those cases when utilising phase sensitive inversion recovery. Only the systolic dyssynchrony index of septal segments allowed differentiation of patient subgroups (artefact/no artefact) and healthy controls ; LBBB with artefact: 10.44% (0.44–20.44%); LBBB without artefact: 6.82% (-2.18–15.83%); controls: 4.38% (1.38–7.38%); Patients with LBBB show recurring artefact patterns in LGE imaging. Use of strain analysis and evaluation of mechanical dyssynchrony may predict the occurrence of such artefacts already during the examination and counteract misinterpretation. A left bundle branch block (LBBB) occurs when conduction through the left bundle branches is slowed down or completely absent, resulting in delayed depolarization of the left ventricular (LV) myocardium . There aIn this internal review board (IRB)-approved study (application number: EA4/192/21), we retrospectively screened all cardiac MRI examinations performed by our centre from 2015 to 2021 for patients with a LBBB, left anterior hemiblock or left posterior hemiblock in an ECG obtained during the period of hospitalisation in which the cardiac MRI examination was performed. A waiver for informed consent was granted by IRB due to the retrospective design of the study. Patients were included in further analysis based on the 2021 European Society of Cardiology criteria, i.e., when the reference ECG showed a widened Q wave, R wave, S wave (QRS) complex of > 120 ms and any other ECG characteristics of an LBBB . At the Cardiac MRI was performed either on a 1.5T or a 3T MRI system . Acquisition of localizers was followed by retrospectively gated 2D steady-state free precession (SSFP) pulse sequences in double-angulated long-axis  and contiguous short-axis slices from the level of the annulus of the mitral valve to the LV apex . Slice thickness was 5 mm for long-axis acquisition and 8 with 2 mm interslice gap for short-axis acquisition. Reconstructed temporal resolution was 35–44 ms. Late gadolinium enhanced images in long-axis  and short-axis views covering the whole LV were acquired 10–12 min after administration of 0.15 mmol/kg gadobutrol  using an inversion-recovery-prepared T1-weighted gradient echo sequence with a manually adjusted inversion time (TI) based on the TI scout as well as a parallel utilised phase-sensitive inversion-recovery (PSIR)-based reconstruction algorithm .Cardiac MRI datasets were evaluated by two board-certified radiologists with eight (*blinded*) and over fifteen (*blinded*) years of experience. For allocation of abnormalities and strain analysis, the LV was divided into segments based on the 17-segment model of the American Heart Association . CINE im® . The endocardial and epicardial contours were automatically registered by the software on short-axis CINE images covering the left ventricle. All contours were checked by two experienced readers. Whenever manual correction of the contours was necessary, it was performed by consensus by the readers. The global SDI , defined as the standard deviation of the segmental time to maximum strain for segments 1–16 normalised to the length of the cardiac cycle and given in time percentage, was used to determine the severity of LV dyssynchrony and to correlate dyssynchrony with the frequency of artefacts identified in LGE imaging septal): defined as the standard deviation of the segmental time to maximum strain for segments 2, 3, 8, 9, and 14 normalised to the length of the cardiac cycle and given in time percentage.Septal SDI (SDI(2)free wall): defined as the standard deviation of the segmental time to maximum strain for segments 5, 6, 11, 12, and 16 normalised to the length of the cardiac cycle and given in time percentage.Free wall SDI , (2) patients with inhomogeneous suppression on TI scout and/or LGE imaging artefacts (LBBBartefact), and (3) healthy controls. Demographic data, QRS width, left ventricular function parameters and systolic dyssynchrony indices were tested for normal distribution within each subgroup  using the Shapiro–Wilk test, homogeneity of variances was asserted using Levene’s Test. In case of normal distribution of parameters, a one-way ANOVA was conducted, and Tukey’s or Games-Howell test was performed as a post hoc test depending on whether a variance equality could be assumed or not. If normal distribution could not be assumed for subgroups, non-parametric testing was performed with the Kruskal–Wallis test and Dunn’s test was performed as a post hoc test. Multiple comparisons were corrected for using the Bonferroni-Holm method. Systolic dyssynchrony indices in patients with LGE were compared using a t-test. If a significant difference was found between the subgroups, a receiver operating characteristic (ROC) curve analysis was performed to measure the diagnostic ability of the respective strain index. The optimal cut-off for separating LBBBartefact and LBBBno artefact was determined using the Youden index. A χ2-test for association was conducted between LBBBartefact and LBBBno artefact and occurence of apical rocking and septal flash. A p-value < 0.05 was considered statistically significant. Descriptive statistics are given as median (median ± interquartile range). SPSS 27 for Windows  was used for statistical analysis.For statistical analysis, three subgroups were defined: (1) patients with no inhomogeneous suppression on TI scout and no LGE imaging artefacts (LBBBp = 0.24), the median duration of the QRS complex was longer in LBBBartefact  than in LBBBno artefact , median duration of the QRS complex in controls was 88 ms (80–96 ms) Regarding global left ventricular function, LVEF was significantly lowered in LBBBartefact when compared to LBBBno artefact and controls (each p < 0.05). Concomitantly, LVEDV and LVESV were significantly higher in LBBBartefact when compared to both other groups (each p < 0.05).A total of 55 patients  with LBBB and 62  controls were included. The median age of patients with LBBB was 57 years (34–80) whereas the median age of controls was 28 years (18–38). A summary of demographic and clinical data as well as global left ventricular function parameters, separately for patients and controls, can be found in In 37 of 55 patients with LBBB (67%), there was no homogeneous nulling of the left ventricular myocardium in the TI scout . In thesseptal was able to differentiate between all three subgroups regarding the extent of left ventricular dyssynchrony , followed by LBBBno artefact  and controls  (each p < 0.05). SDIglobal was highest among LBBBartefact with 10.16% (2.16–18.16%). SDIglobal was generally able to differentiate between patients and controls (each p < 0.05), but could not distinguish between LBBBartefact and LBBBno artefact and therefore could not estimate the occurrence of artefacts in LGE imaging. SDIfree wall was highest among LBBBno artefact with 4.67% (1.67–7.67%), but could not distinguish between the different groups. Regarding the occurrence of artefacts, ROC analysis revealed an area under the curve of 0.863 for SDIseptal with an optimal cut-off value of 7.36% . Furthermore, SDIseptal was able to distinguish between LBBBartefact and LBBBno artefact in patients with LGE , whereas SDIglobal and SDIfree wall were not able to differentiate between these subgroups if LGE was present. All dyssynchrony indices did not significantly differ between patients with LBBB and LGE and patients with LBBB without LGE (p = 0.077–0.993). Septal flash and apical rocking occurred more often in LBBBartefact with 70 and 62%, respectively, versus 33 and 17% for LBBBno artefact (each p < 0.05). None of the controls showed these features of dyssynchrony. There was no significant difference between patients with LBBB and LGE and patients with LBBB without LGE in terms of occurrence of septal flash and apical rocking (p = 0.37 respectively p = 0.944).A summary of strain analysis and additional parameters of mechanical dyssynchrony is given in ynchrony . SDIseptThe results of our study show that artefacts are common in LGE imaging of patients with LBBB and exhibit recurring patterns. While artefacts in TI scout and LGE images may be identified as such by trained observers, they are potential sources of error in clinical routine when imaging findings are reported by possibly less experienced readers, and this may have an impact on further treatment planning especially when the extent of scar tissue is then overestimated , 23.artefact exhibited apical rocking and septal flash than in LBBBno artefact, suggesting that the risk for the occurrence of artefacts can be assessed already based on these two characteristics. However, a segmental and therefore more precise analysis of the extent of mechanical dyssynchrony can be achieved using strain analysis. Rutz et al. reported that a circumferential SDI  was highest among patients with LBBB and identified most severe dyssynchrony compared to controls and patients with myocardial infarction  sequence , 25. Firfarction . While tsegments , 33. Thecibility . ConsideTo the best of our knowledge, this is the first study that has systematically analysed the occurrence of specific artefacts in this relatively common form of conduction delay. However, despite the potential utility of our results for routine clinical practice, some limitations need to be considered. First, due to the retrospective design of the study, it was not possible to form different subgroups  with sufficiently large numbers of patients for a more differentiated analysis of possible factors influencing dyssynchrony. Comparable studies included groups of 20–43 patients , 14, 34.Patients with LBBB show recurring artefact patterns on cardiac MRI in both TI scout and LGE images, which may compromise the quality of cardiac MRI but also of subsequent reporting if readers are not familiar with these artefacts. The qualitative and quantitative analysis of left ventricular dyssynchrony may assist estimate the occurrence of such artefacts already during the MR examination and may help avoid misinterpretation.The datasets used and/or analysed during this current study are available from the corresponding author on reasonable request.This study was approved by the Internal Review Board of Charité-Universitätsmedizin Berlin . Application number: EA4/192/21. A waiver for informed consent was granted by IRB due to the retrospective design of the study.AP made substantial contributions to the design of the study, the strain analysis, interpretation of data and drafting the manuscript. SN and BH made substantial contributions to drafting the manuscript. TE made substantial contributions to the design of the study, analysing late gadolinium enhancement images, the interpretation of data and drafting the manuscript. L-AS made substantial contributions to the design of the study, strain analysis, analysing late gadolinium enhancement images, the interpretation of data, drafting the manuscript and has agreed to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature. All authors contributed to the article, agree to be accountable for their contributions, and have approved the submitted version.


Background and Objectives: Patients with surgical aortic stenosis (AS) show impaired diastolic filling, which is a risk factor for early and late mortality after aortic valve replacement (AVR). There is a paucity of information concerning the impact of restrictive diastolic filling and the evolution of diastolic dysfunction in the early and medium terms post-AVR. We aimed to determine the prognostic value of the presence of a restrictive left-ventricular (LV) diastolic filling pattern (LVDFP) and dilated left atrium (LA) in patients with AS and LV systolic dysfunction (LVEF < 40%) who underwent AVR, and to define the independent predictors for immediate and long-term prognosis and their value for preoperative risk estimation. Materials and Methods: The study was prospective and included 197 patients with surgical AS and LVEF <40% who underwent AVR. Preoperative echocardiographic examinations were repeated at day 10, at 1, 3 and 6 months, and at 1 and 2 years after surgery, with evaluation of LVEF, diastolic function and LA dimension index (mm/m2). Depending on LV systolic performance, patients were classified as Group A (LVEF: 30–40%) or Group B (LVEF < 30%). Results: The main echographic independent parameters for early and late postoperative death were: restrictive LVDFP, significant pulmonary hypertension, LV end-systolic diameter (LVESD) >55 mm and the presence of second-degree mitral regurgitation. Restrictive LVDFP and LA dimension >30 mm/m2 were independent predictors for fatal outcome (p = 0.0017). Conclusions: Assessment of diastolic function and LA dimension are reliable parameters in predicting fatal outcome and hospitalization for heart failure, having an independent and incremental prognostic value in patients with surgical AS. Complete evaluation of LVDFP with all the echographic measurements (including TDI) should routinely be part of the preoperative assessment of patients with LV systolic dysfunction undergoing AVR. The most frequent cardiovascular diseases that affect the elderly population are: hypertension, coronary artery disease and aortic stenosis (AS), which is also the most common valvular heart disease . Its preThe risk of myocardial-infarction- and cardiovascular-caused death is increased by 50 percent if AS is associated, despite the non-hemodynamically significant obstruction of the LV outflow tract ,4.As long as the increased wall thickness can compensate the high systolic pressure from the inside of the LV, the systolic function of the LV in patients with AS will be preserved . If the Although many studies on diastolic dysfunction have been published, there is a paucity of information on diastolic dysfunction evolution in the early and medium terms after aortic valve replacement. Only a few studies have evaluated the real impact of the type of LV diastolic filling pattern (LVDFP) on early postoperative evolution in patients with surgical AS ,11. PrevTo address these issues, we studied a series of patients undergoing AVR for chronic AS. Severity of disease was estimated by symptoms, clinical evaluation, echocardiography and cardiac catheterization. The main objective of our study was to assess the immediate prognostic implications of the LVDFP in patients with AS undergoing AVR. We also identified the echographic parameters which can be considered independent predictors for short- and long-term outcomes in these patients and their adjusted values for the evaluation of preoperative risk.We performed a prospective study of 197 adult patients (mean age: 70 ± 12 years) with surgical AS, diagnosed by two-dimensional and Doppler transthoracic echocardiogram and LVEF <40% (mean LVEF: 28 ± 5%), who underwent AVR. Patients were evaluated clinically and by heart ultrasound before the surgical intervention and at 10 days and 1, 3, 6, 12 and 24 months postoperatively. For each patient, systolic and diastolic LV performance were evaluated, along with LA function, the severity parameters of AS and the dimensions of the heart chambers. Written informed consent was obtained from all patients. Patients were asked by letter to agree to follow-up visits on an ambulatory basis. The study protocol was approved by the local ethics committee.To assess the independent prognostic value of the presence of a restrictive mitral flow pattern and dilated LA in patients with surgical AS and altered LV systolic function undergoing AVR.To determine short- and long-term-prognosis echographic independent predictors, with their adjusted values used for preoperative risk evaluation.-Type of LVDFP;-Quality of life ;-Death.We analyzed the following endpoints:We evaluated global quality of life, including a mental component (MCS) and a physical component (PCS), using a self-report questionnaire. The scores were continuous from 0 (lower) to 10 . Patients outlined their change in quality of life at the 30-day follow-up questionnaire by answering from both points of view, mental and physical, the question: “How would you rate your quality of life now?”. The answer choices were: “Worse than before your procedure”, “The same as before your procedure” and “Better than before your procedure”.-Associated or previous mitral or tricuspid valve replacement or repair;-Aortic dissection;-Previous aortic valve surgery;-Congenital diseases unrelated to AS;-Coronary significant lesions ;-Postoperative prosthesis mismatch;-Permanent atrial fibrillation;-Presence of a pacemaker;-Left or right bundle-branch block.Exclusion criteria:Patients undergoing concomitant procedures, such as associated ascending aortic surgery with AVR, were not excluded.-Group A—136 pts, with moderate systolic dysfunction and LVEF = 30–40%;-Group B—61 pts, with severe systolic dysfunction and LVEF <30%.Depending on LV systolic performance, the patients were divided into two groups:The diagnosis of AS was performed using primary hemodynamic parameters recommended for evaluation: AS jet velocity, mean transaortic gradient and the valve area by continuity equation  Table 1Table 1.All echocardiographic examinations were performed with a Philips Affinity 30 or a portable General Electric VIVID machine, with a 3.5 MHz probe. Echocardiographic techniques and calculations were performed in accordance with the recommendations of the European and American Society of Echocardiography .The parameters assessed at each visit were: LV systolic and diastolic performance (including TDI measurements), LA indexed volume, aortic prosthesis hemodynamic parameters and dimensions of the heart cavities  .Left-ventricular ejection fraction (LVEF) was calculated using a modified Simpson’s method. The assessment of diastolic function was based on a comprehensive echocardiographic study integrating all available two-dimensional and Doppler data. By placing the pulsed-wave Doppler between the mitral leaflet tips in the apical four-chamber view, we could record the transmitral flow. We measured the transmitral peak early-diastolic (E) and late (A)-flow velocities, the E/A ratio and the deceleration time (EDt) . To calc-Peak annular systolic velocity (Sa) as the peak negative systolic wall motion wave at the level of the T-wave of the ECG;-Early-diastolic velocity (Ea), which reflects the velocity of early myocardial relaxation as the mitral annulus ascends during early rapid LV filling;-Late-diastolic (Aa) velocity.We also performed tissue Doppler imaging (TDI) by recording myocardial longitudinal velocities at the mitral annulus, with the sample volume (2–5 mm) placed at the lateral border of the mitral annulus in the apical four-chamber view for estimation of LV filling pressures. The lateral mitral annulus was aligned parallel to the sampling cursor, and the sweep speed was set at 50 mm/s. The spectral Doppler-signal filter settings were adjusted at the lowest wall filter and at the minimum optional gain. We measured:The classification of the diastolic function was: normal , impaired relaxation , pseudonormalization  and restrictive pattern  .All patients over 35 years of age, as well as patients under 35 years old with angina pectoris, underwent arteriography. None of the patients had associated coronary artery disease . For patients presenting with symptoms suggestive of heart failure and preserved systolic function, brain natriuretic peptide (BNP) titration was performed. Diastolic heart failure was considered unlikely for values under 35 pg/mL and possible if values surpassed 100 pg/mL.t-test, while data between three groups were tested with analysis of variance (ANOVA) and Tukey’s post hoc test, assuming equal variances, and the Games–Howell post hoc test, assuming nonequal variances between the groups. The Wilcoxon test and the Friedman test were used to compare preoperative and postoperative echocardiographic variables. Statistical analyses were performed using SYSTAT and the Statistical Package for the Social Sciences 11.5 (SPSS 11.5) software. Continuous variables were indicated as means ± standard deviations, and qualitative data were recorded as percentages. Categorical variables were tested using the Pearson chi-square test, likelihood ratios and Fisher’s exact test, and quantitative data between the two groups were tested with the independent-samples The association between preoperative variables and postoperative change in LVEF was based on Pearson correlation analysis, and linear regression analysis was used to establish the associations between preoperative data and the parameters associated with postoperative evolution . Univariate logistic regression analysis was used to compare the two groups. Multivariate logistic regression analysis was performed to identify predictive factors of mortality. Areas under the receiver-operating-characteristic (ROC) curves and Hosmer–Lemeshow goodness-of-fit statistics were calculated to assess the discrimination and calibration of the model, respectively. To evaluate the goodness-of-fit of the model, Cox–Snell/Nagelkerke values were calculated. A probability value of <0.05 was considered statistically significant.We tested two main hypotheses. The first was that LA dilatation and restrictive LVDFP are independent predictors for unfavorable postoperative evolution in patients with AS and LV systolic dysfunction undergoing AVR. The second hypothesis tested was that the presence of restrictive LVDFP makes a higher contribution than LV systolic dysfunction to preoperative risk calculations for patients with AS undergoing AVR. For hypothesis testing, we used univariate and multivariate logistic regression analysis, correlation-coefficient calculations and nonparametric Friedman testing .p < 0.005, likelihood ratio). In addition, at 30 days postoperatively, 60,29% of patients from group A reported a better postoperative quality-of-life score compared with only 36.06% in group B with preoperative severe LV systolic dysfunction . Taking into account the postoperative course of the study groups, we calculated the overall percentage of patients whose self-reported quality-of-life scores (SR QOL scores), changed between better/the same/worse . In group A, 48.53% of patients had a preoperative self-reported quality-of-life score less than 5 compared to 85.24% of patients from group B (p = 0.06) and significant improvement in group A (p = 0.002). Postoperative end-diastolic and end-systolic dimensions decreased significantly in both groups (Postoperative echocardiography showed a trend toward improvement in LVEF in group B (h groups .p = 0.001), regardless of LV dimensions and systolic function, patient age, comorbidities and presence of pulmonary hypertension  increased the risk of death early after surgery, regardless of the presence of other parameters known to increase mortality rates in patients with AS undergoing surgical treatment. The analysis of the two groups, depending on the type of LVDFP, revealed that the restrictive LVDFP turned out to be an independent predictor for increased early mortality rates in these patients , but mostly in those with restrictive LVDFP. The prognostic value of LA dilatation decreases if there is a concomitantly pulmonary hypertension or a second-degree mitral regurgitation. In these patients, the presence of LA dilatation was not correlated with a higher early postoperative mortality rate . In addition, the index of LA dimension >30 mm/mThe presence of a restrictive LVDFP homogenized the relative risk. In patients with this type of filling pattern, early postoperative risk of death was increased regardless of LV systolic performance, patient age or the presence of LV hypertrophy with an interventricular septum thickness between 12 and 18 mm. Severity of AS and LV diastolic dimensions were not correlated with increased early postoperative mortality.-p < 0.05);The presence of second-degree MR ;Isovolumetric relaxation time <60 ms ;E-wave deceleration time <100 ms ;S/D ratio <1 in pulmonary venous flow ;Mean pulmonary artery pressure >50 mmHg .LV end-systolic diameter (LVESD) >55 mm .Parameters of LV systolic function, end-systolic and end-diastolic diameters and volumes, as well as parameters of aortic lesion severity  were not correlated with increased early postoperative mortality in these patients .The cut-off value for E-wave deceleration time <100 ms was estimated using both the classical method of two standard deviations from the difference between the mean values for restrictive and non-restrictive LVDFP and ROC curves, taking into account the maximization of sensitivity. For an E-wave deceleration time <150 ms, the associated relative risk was only 5.6, and it was not significantly correlated with postoperative mortality .The relative risks associated with early postoperative death and the parameters which increase mortality rates in AS are presented in p < 0.01), end-diastolic volume >85 cm3 , restrictive LVDFP  and LV eccentric hypertrophy . Patients with LV concentric hypertrophy had a better prognosis than patients with eccentric hypertrophy .The factors associated with unfavorable evolution in patients with AVR at 2 years after surgery revealed by multivariate logistic regression analysis were: age >75 years . Taking into account the presence of a restrictive LVDFP, Friedman testing showed that it has a significantly higher influence on quality-of-life score at 2 years postoperatively compared with LV systolic severe dysfunction (LVEF <30%). The percentage of patients with a better postoperative quality-of-life score in the nonrestrictive LVDFP group was 72.22% compared with only 17.07% in the group with preoperatively restrictive LVDFP .Regarding self-reported quality of life at 2 years postoperatively, the percentage of patients with a better postoperative quality-of-life score in group A was also significantly higher compared with group B  [It was reported that patients with an LA diameter of less than 3.55 cm had increased long-term survival compared to patients with a severely enlarged LA (≥5.0 cm in diameter) at 5 (85% vs. 61%) and 10 (62% vs. 28%) years after AVR (= 0.006) . Preoper= 0.006) . Left-at= 0.006) . 2 for group A and >32 mm/m2 for group B were found to be independent predictors for fatal outcome .In our study, the indices of LA dimension >30 mm/mA study directed by Milano et al. emphasized that increased LV diameter and reduced LV function in patients with severe AS were associated with percentage of myocardial fibrosis, influencing long-term survival after AVR. These patients were found to have an increased risk of cardiac death at 10 years postoperatively as a result of congestive heart failure .Moderate-to-severe diastolic dysfunction is still seen after 10 years post-AVR, despite reduction in LV mass index, according to Gjertsson et al. .There is a relative increase in LV fibrous content soon after AVR and a relative reduction after 4 to 5 years, these changes occurring as part of a two-step process, with the regression of LV interstitial fibrosis leading to the reversal of LV diastolic function ,29.We noticed in our study that LV end-systolic diameter (LVESD) >55 mm was an echographic predictor of early postoperative mortality in patients with surgical AS and LV systolic dysfunction.The exposure of the heart to ischemia and reperfusion after AVR may result in the worsening of systolic or diastolic dysfunction , requiriElevated end-diastolic pressure is common in surgical AS and is related to pulmonary artery hypertension. Early and late outcomes after valve replacement are affected by the presence of pulmonary hypertension, which is considered a significant risk factor . OperatiThe prognoses of patients with AS and severe pulmonary hypertension are very poor among patients treated conservatively , and AVROn the other hand, management of mitral regurgitation (MR) during AVR for AS of intermediate degree is still controversial. The associated MR in patients undergoing AVR is frequently not corrected because it may improve after AVR. However, it was proved that the reduction in MR after relief of AS is modest and that gradient change across the aortic valve has very little impact on the reduction in MR . The impRegarding quality of life, we observed that, although the patients with restrictive LVDFP survived, they performed much worse compared to the patients with the non-restrictive pattern, the presence of a restrictive LVDFP having a greater influence on the postoperative course compared with LV severe dysfunction.However, defining the thresholds for a marked reduction in LV diastolic function in patients with surgical AS in order to calculate a preoperative risk score remains an unresolved issue. Our study provides evidence that severe diastolic dysfunction, in addition to LA dilatation, identifies patients at risk of poor prognosis after valvular aortic surgery. Clinicians should identify high-risk cardiac patients with the use of perioperative echocardiograms in ICUs and improve fluid and inotropic/lusitropic drug treatments postoperatively to provide proper treatment.Preoperative diastolic dysfunction related to adverse cardiac outcome brings into question whether trials of specific perioperative strategies to enhance LV relaxation and filling patterns should be taken into account in patients undergoing AVR.In spite of this being one of the largest studies on tissue Doppler evaluation of diastolic filling in surgical AS, the patient number was still average.Additionally, AVR, for all the patients in our study, was surgical and we did not have a comparison group of patients who underwent transcatheter aortic-valve implantation.In summary, this study emphasizes that, for patients undergoing AVR, a full evaluation of diastolic function should routinely be part of echocardiographic assessment. The presence of a restrictive LVDFP can predict fatal outcome and heart-failure hospitalization in patients with surgical AS and LV systolic dysfunction undergoing AVR.In these patients, LA dilatation had an incremental and independent prognostic value for early postoperative course assessment. In addition, a more reliable parameter for prognosis appreciation is LV diastolic performance compared with LV systolic function.The presence of associated severe pulmonary hypertension or second-degree mitral regurgitation decreases the prognostic value of LA dilatation and increases mortality rates.The presence of a restrictive LVDFP and severe pulmonary hypertension, second-degree mitral regurgitation and dilated LV with LVESD >55 mm can echographically anticipate augmented early postoperative mortality rates in patients with surgical AS and LV systolic dysfunction.3 and the restrictive LVDFP were the only predictors for unfavorable evolution. Quality of life early and at 2 years post-AVR was significantly influenced by the presence of a restrictive LVDFP, which was more important than severe LV systolic dysfunction in prognostic prediction. At 2 years postoperatively, age >75 years, LVESV >85 cmPatient stratification has to take into account diastolic function in the first place, then heart-chamber dimensions, pulmonary hypertension and LV systolic performance. In order to calculate the preoperative risk score, it is very important to introduce guidelines regarding the presence of a restrictive pattern, which is as important as age and comorbidities in establishing prognoses. Present guidelines do not include pulse-wave and TDI diagnosis of the restrictive pattern in preoperative risk evaluation, and future updates could be necessary.