Postcardiotomy extracorporeal membrane oxygenation (PC-ECMO), the most frequent indication for ECMO in the United States, is increasingly used as the first-line mechanical circulatory support in patients who are refractory to conventional treatment. Despite increasing use of PC-ECMO, limited evidence is available regarding its safety, efficacy, and optimal timing for initiation and weaning. The decision to use PC-ECMO often is made in the absence of robust clinical data, leading to variability in patient selection, management, and outcomes across different institutions. This article summarizes current evidence on ECMO use in postcardiotomy cardiogenic shock and discusses its potential benefits, management, complications, and outcomes. Postcardiotomy cardiogenic shock (PCCS) occurs in 2% to 6% of patients undergoing surgical revascularization or valvular surgery.8In 1966, Michael DeBakey used the first left ventricular assist device (LVAD) to support a patient who was in refractory PCCS. Following the first heart transplantation by Christiaan Barnard in 1967 and widespread acceptance of transplantation, MCS devices have been regularly used to sustain those patients in refractory PCCS to allow time for decisions regarding further management with implantable devices or heart transplantation.9 It is increasingly used as first-line MCS in patients who are refractory to conventional treatment. PC-ECMO facilitates respiratory gas exchange and provides cardiac output to end organs, supporting organ recovery and allowing time for “bridge-to-decision” to more durable modes of support.11PC-ECMO has become the most frequent indication for ECMO in the United States (US).The published reports of PC-ECMO are mostly single-center experiences. Despite increasing use of PC-ECMO, there is limited evidence on its safety, efficacy, and optimal timing of initiation and weaning. The decision to use PC-ECMO is often made in the absence of robust clinical data, leading to variability in patient selection, management, and outcomes across different institutions. Moreover, PC-ECMO is associated with a high risk of complications, which can further impact patient outcomes and healthcare costs. In this article, we aim to summarize the current evidence on ECMO use in PCCS and discuss its potential benefits, management, complications, and outcomes.12The nature of the PC-ECMO indication is that patients invariably require urgent or emergent ECMO support compared with other indications. Patients requiring PC-ECMO are usually older, with a higher incidence of renal insufficiency, prior myocardial infarction, left main coronary artery disease, and left ventricular (LV) dysfunction. They also are more likely to have a prolonged history of coronary artery disease and prior open-heart surgery.16PC-ECMO is most frequently associated with patients who undergo coronary artery bypass grafting (CABG) (26.8%) and valve surgery (25.6%) followed by post-heart transplantation (20.7%). The use of ECMO in post-heart transplant recipients has been reported to be as high as 10% to 15% of patients.The most common indication for PC-ECMO implementation is intraoperative failure to wean from cardiopulmonary bypass (CPB) because of univentricular, biventricular, or delayed refractory cardiogenic shock; postoperative cardiac arrest in the intensive care unit (ICU); respiratory failure; or intractable postoperative ventricular arrhythmias.16 Another indication for PC-ECMO is in patients who develop right ventricular failure after LVAD implantation. PC-ECMO may be utilized to support the right ventricle (RV) or to bridge to an RV assist device.18PC-ECMO is also used for early graft dysfunction in post-heart transplant recipients.19The use of ECMO for PC cardiac arrest has been increasingly implemented during the last 10 years. The 2020 European Association for Cardio-Thoracic Surgery/Extracorporeal Life Support Organization/Society of Thoracic Surgeons/American Association for Thoracic Surgery Expert Consensus for the Resuscitation of Patients who arrest after Cardiac Surgery recommended that failure to achieve spontaneous circulation is an indication for open cardiac massage and the institution of either central or peripheral ECMO at the bedside.Operating room (OR) cannulation, either centrally or peripherally, occurs most frequently, followed by the ICU and rarely on the ward. Most PC-ECMO placements occur within 24 to 48 hours of procedure, and patients are rarely supported on ECMO for more than 15 days.The choice of ECMO cannulation site depends on several factors, including timing, indication, urgency of deployment, and the need for cardiocirculatory or respiratory support as well as institutional considerations such as staff familiarity and availability of ECMO circuits.9When opting for central PC-ECMO cannulation, an open sternum is typically required to accommodate the atrial and aortic cannulas. This approach provides improved cardiac decompression and anterograde flow from the proximal aorta compared to peripheral cannulation, thereby mitigating the potential complications associated with retrograde flow, such as “Harlequin syndrome.” However, it is worth noting that central cannulation is associated with higher rates of bleeding and renal failure .99Innovative strategies have been developed to address the management of atrial and aortic cannulas in central cannulation. These strategies involve sternal closure with tunneled cannula exit either in the subxiphoid or suprasternal region. Such approaches offer several benefits, including facilitating patient extubation and mobilization, while reducing the risk of infection .920Venoarterial ECMO (VA-ECMO) is effective in draining the right side of the heart but may not adequately decompress the LV due to incomplete drainage of systemic and bronchopulmonary venous flow. This can lead to LV distension caused by impaired LV contractility or high afterload, resulting in inadequate ejection. In turn, insufficient LV ejection can cause blood stasis in the left cardiac chambers, increasing the risk of clot formation and catastrophic consequences. To mitigate these risks, the use of MCS devices for LV unloading is increasingly considered. Clinical studies and literature analyses suggest improved outcomes when adjunctive LV unloading strategies are employed.20Various indirect and direct modalities for LV unloading have been described, including intra-aortic balloon counterpulsation pump (IABP), Impella, atrial transseptal catheterization, atrial septostomy, pulmonary artery drainage/venting, transaortic venting, and direct left atrial and LV venting.23The use of IABP in conjunction with VA-ECMO is a topic of debate. When combined with VA-ECMO, IABP is employed to improve coronary perfusion and support LV ejection and blood flow pulsatility by reducing afterload and LV wall tension, thereby decreasing blood stasis in the left heart. The concomitant use of IABP with PC-ECMO does not appear to increase the risk of limb ischemia.27Several clinical studies have investigated the role of Impella for unloading/venting in VA-ECMO-treated patients with cardiogenic shock. Pappalardo et al. described a large series of patients treated with the combination of VA-ECMO and Impella compared to patients treated with VA-ECMO alone. Despite a higher need for continuous renal replacement therapy (48% vs 19%) and increased hemolysis (76% vs 33%), the combination group had significantly lower hospital mortality (47% vs 80%) and a higher rate of successful bridging to recovery or further therapy (68% vs 28%) than the VA-ECMO alone group.28In another international multicenter cohort study involving 686 patients with cardiogenic shock treated with VA-ECMO, the use of LV unloading with Impella during VA-ECMO was associated with lower mortality compared with VA-ECMO support alone (58.3% vs 65.7%).13 Major hemorrhage is the most reported complication after the institution of VA-ECMO. It has led to reintervention in almost half of the patients in some studies.33 Many investigators advocate avoiding heparin infusion for the first 12 to 48 hours provided that high flows are maintained to prevent clot formation.34The use of PC-ECMO is associated with numerous complications, although the number of patients with major complications has decreased in recent years.Central nervous system complications have recently been shown to occur in 15% of adult patients supported with VA-ECMO and 7% of adult patients supported with VV-ECMO.38In PC-ECMO, these rates may be much higher, occurring in up to 30% of patients.34In a single-center retrospective study of 496 PC-ECMOs, neurologic complications occurred in 87 patients (21.0%), including cerebral infarction in 33 (8.0%), brain death in 30 (7.2%), seizures in 14 (3.4%), and intracranial hemorrhage in 11 (2.7%). In-hospital mortality in patients with neurologic complications was 90.8% compared with 52.1% in control patients. Low systolic blood pressure level pre-ECMO and aortic surgery combined with coronary artery bypass grafting were associated with high neurologic complications.39Renal failure requiring renal replacement therapy was another commonly reported complication. The incidence of renal failure requiring renal replacement therapy while on PC-ECMO had a strong association with mortality.35With regard to limb ischemia in peripherally cannulated VA-ECMO, several investigators have consistently reported reduced limb ischemia with the routine use of ipsilateral distal perfusion. A delay in distal perfusion cannula placement, triggered by signs of ischemia, may lead to a reperfusion injury with a poor outcome.41Weaning off ECMO requires a thorough assessment of various parameters. Echocardiographic indices are commonly used to evaluate readiness to be weaned, along with other parameters such as biomarkers or hemodynamic parameters. Signs of persistent organ damage are negatively associated with weaning outcomes. Higher aspartate aminotransferase levels at 48 and 72 hours after ECMO initiation are linked to weaning failure.42 In contrast, successfully weaned patients exhibit favorable right ventricular hemodynamic parameters at 48 and 72 hours, including lower right atrial (RA) pressure to pulmonary capillary wedge pressure ratio, lower transpulmonary gradient, and higher pulmonary artery pulsatility index.43Pulse pressure (PP) less than 30 mm Hg is independently associated with weaning failure.51 Additionally, improvements in lateral e’ velocity and tricuspid annular S’ velocity during a flow reduction trial are predictors of weaning success.35The early recovery of LVEF after VA-ECMO initiation is linked to improved weaning outcomes. The most widely used parameter to track LV recovery in patients on VA-ECMO is the LV outflow tract velocity time integral (VTI), with a threshold of greater than 9.5 cm commonly reported to predict successful weaning.52Ventricular interdependence absence is also a robust predictor of successful weaning, with a sensitivity of 94% and specificity of 95%.2 greater than 65%, absence of ventricular arrhythmia, optimized fluid balance, adequate native lung oxygenation capacity with resolution of pulmonary edema, and an inspired oxygen fraction less than 50%. Echocardiographic improvement in myocardial function is evident by S’ > 6 cm/s, left ventricular ejection time > 200 ms, LV outflow tract VTI = 10 cm, and tricuspid annular plane systolic excursion > 10 mm.35Suggested criteria for weaning from VA-ECMO include maintaining a mean arterial pressure equal or greater than 60 mm Hg with minimal inotropic and vasopressor support, lactate normalization, SvO2, then removal of ECMO can be considered with surgical repair of the mediastinum or the peripheral vascular access. Some centers recommend maintaining EC blood flow at between 1.5 and 2 L/min for 24 h with hemodynamic stability prior to ECMO removal.Once these criteria are met, a gradual reduction of ECMO blood flow to 0.5-1 L/min  with careful monitoring of hemodynamics, vasopressor needs, and biventricular response to load variation can be initiated. When this is achieved, the arterial and venous lines can be clamped for 1 to 2 min (on therapeutic anticoagulation). If the LV ejection fraction was >35% to 40%, VTI was > 10 cm, and cardiac index (CI) was > 2.2 L/min/m35 which reduces the risk of circuit thrombosis. During PCRTO, pump speed is gradually reduced until the flow becomes retrograde, creating a controlled arteriovenous fistula. Retrograde flow is maintained for up to 1 hour, during which time the sweep gas is turned off to assess any residual gas exchange impairment. If the patient remains stable, and hemodynamic parameters, vasopressor needs, and oxygen requirements remain within acceptable ranges, the trial is considered successful. It is important to note that reversing the flow during PCRTO comes with a theoretical risk of pulmonary embolism through clot detachment from the venous side of the oxygenator. Further studies are necessary to validate the safety and efficacy of this weaning method.53The use of pump-controlled retrograde trial off (PCRTO) instead of circuit clamping has been reported,13Analysis of the Extracorporeal Life Support Organization (ELSO) registry for patients on PC-ECMO from January 2010 through December 2018 showed that successful weaning from ECMO was possible in 56.4% of patients, while survival to hospital discharge was achieved in 41.7% of cases. Higher mortality was observed after CABG (65.4%), combined CABG with valve (68.4%), and aortic procedures (69.6%) when compared with other indications. Lower mortality rates were observed in heart transplantation recipients (46.0%).54Pozzi et al. described similar outcomes in 90 patients who required PC-ECMO between January 2007 and December 2017 in France; in this report, successful weaning was accomplished in 50% of patients after a mean support 6.4 days, and 39% of patients survived to hospital discharge.13Older age is significantly associated with hospital death. Patients over 70 years of age had lower survival rate to discharge compared with those ≤ 70 years old.56 A trend toward lower in-hospital mortality was reported with peripheral VA-ECMO cannulation compared with central cannulation.13In several experiences, extracorporeal cardiopulmonary resuscitation (ECPR) is a strong negative predictor of survival.7 Another study found that a pre-ECMO implantation lactate level of greater than 6.45 mmol/L was associated with higher mortality. Patients who showed decreasing lactate after PC-ECMO support had higher success rates of weaning off ECMO.The timing of PC-ECMO implementation before organ hypoperfusion progresses is very important. Fux and collaborators have shown that a lactate value above 10 mmol/L at implant is associated with 90% in-hospital mortality, with no survival when lactate levels were > 15 mmol/L.ECMO has been increasingly used to support patients with refractory PCCS, which is invariably a fatal clinical state. Despite advancements in ICU management and ECMO circuit components and technologies, mortality rates have not significantly decreased over time. Further improvement in patient selection, early implantation of ECMO before tissue hypoperfusion, LV unloading, cannulation approach, anticoagulation protocols, and ECMO management are important to improve these patients’ outcomes.


Diastolic stiffness coefficient (β) and end‐diastolic elastance (Eed) are ventricular‐specific diastolic parameters. However, the diastolic function of right ventricle had not been investigated sufficiently due to the lack of established evaluation method. We evaluated the validity of these parameters calculated using only data of right heart catheterization (RHC) and assessed it in patients with restrictive cardiomyopathy (RCM) and cardiac amyloidosis. We retrospectively analyzed 46 patients with heart failure who underwent RHC within 10 days of cardiac magnetic resonance (CMR). Right ventricular end‐diastolic volume and end‐systolic volume were calculated using only RHC data, which were found to be finely correlated with those obtained from CMR. β and Eed calculated by this method were also significantly correlated with those derived from conventional method using CMR. By this method, β and Eed were significantly higher in RCM with amyloidosis group than dilated cardiomyopathy group. In addition, the β and Eed calculated by our method were finely correlated with E/A ratio on echocardiography. We established an easy method to estimate β and Eed of right ventricle from only RHC. The method finely demonstrated right ventricular diastolic dysfunction in patients with RCM and amyloidosis. Unfortunately, they are often influenced by several confounding factors, such as preload and afterload, and may not reflect ventricular‐specific function  is one of the most reliable tests for hemodynamic evaluation in heart failure patients, and it greatly assists in determining treatment strategies in clinical practice , which is formed by simultaneously measuring the pressure and volume in the ventricle and plotting them in the same plane, is useful for evaluating heart failure and pulmonary hypertension. Therefore, many studies focused on end‐systolic pressure‐volume relationship (ESPVR) and end‐diastolic pressure‐volume relationship (EDPVR) derived from the PV loop as indices that can evaluate ventricular intrinsic contractility/dilatability independent of preload.In order to apply the PV loop in clinical practice, it is desirable to estimate multiple PV loops using the conductance catheter in the ventricle and to change the preload by occlusion of the inferior vena cava or other means such as the multiple‐beat method  and amyloidosis, which are representative of diastolic dysfunction.22.1Heart failure patients admitted to our institution from January 2019 to May 2022 who underwent RHC within 10 days of CMR scans were retrospectively included. Patients with moderate or severe tricuspid, or pulmonary valve regurgitation, or congenital heart disease were excluded because such conditions render the premise of the isovolumic range of the single‐beat method invalid. The University of Tokyo Institutional Review Board reviewed and approved this study protocol conformed to the tenets of the Declaration of Helsinki . Informed consent was obtained in the form of an opt‐out selection on our web‐site.2.2After local anesthesia, a 7‐Fr ballooned Swan–Ganz catheter (Edwards Lifesciences) was inserted through the internal jugular vein and right atrial pressure, right ventricular pressure (RVP), pulmonary artery wedge pressure, and pulmonary artery pressure (PAP) were measured. RVP waveform was recorded with breath‐holding during the expiratory phase. Moreover, cardiac output (CO) and cardiac index (CI) were measured in all cases using thermodilution and the indirect Fick method. The stroke volume (SV) was obtained by dividing CO by heart rate.Blood tests were performed at the time closest to the date of RHC. Echocardiography was also performed at the time closest to the date of RHC and normal echocardiographic parameters, including left ventricular ejection fraction (LVEF), E/A ratio , E/e’ ratio , right ventricular fraction area change (RVFAC), and tricuspid annular plane systolic excursion (TAPSE) were evaluated.2.32; matrix, 128 × 128; reconstruction matrix, 256 × 256). RV volume was calculated using AZE virtual place system (AZE). To obtain the RV volume, endocardial borders of the RV were manually traced to calculate end‐systolic volume (ESV) and end‐diastolic volume (EDV).All CMR images were obtained using 3 Tesla MRI system . Cine sequences were obtained using ECG‐triggered, balanced turbo field echo (bTFE) sequence in left ventricular long axis images and short axis images from base to apex (echo time (TE) / repetition time (TR): 1.41 ms (four‐chamber view), 1.29 ms (two‐chamber view), 1.37 ms (short axis)/2.8 ms; flip angle (FA), 50°; slice thickness, 10 mm; FOV, 380 × 380 mm2.42.4.1max)  is the slope of the ESPVR line, and arterial elastance (Ea) is defined by ESP/(EDV‐ESV).Based on single‐beating method of Sunagawa et al, ESPVR is defined by a straight line passing through the two points  and , , and   .P = α (eThe β derived from this equation was defined as the diastolic stiffness.The end‐diastolic elastance (Eed) was calculated using the following equation  and comma‐separated values of the consecutive 10–15 RVP waveforms at a sampling rate of 1000 Hz were extracted. We analyzed 3 waveforms to be measured stably of them, using MATLAB software . The range of IC and IR in the RVP waveform during one cycle was designated, and a sine‐curve fitting using the Levenberg–Marquardt least square algorithm was performed with the maximum value of the sine curve as P2.4.3max, ESP, and SV.Assuming that the ESPVR passes through , the ESV and EDV were calculated from the three values of PmPAP using mean pulmonary artery pressure (mPAP) and ESPmodified derived from the following equation  − mPAP) × (time to RVSP − time to dP/dt max)/(time to dP/dt min − time to dP/dt max)] , , and  .Data are expressed as means with standard deviations or medians with interquartile ranges. We used the Shapiro–Wilk test to assess the normality of data distribution. We also used the Student's t‐test or Mann–Whitney 33.1A total of 53 patients were enrolled in this study from January 2019 to May 2022. Seven patients were excluded because of the unclear pressure waveforms, inability to perform a stable pressure assessment due to large respiratory variability, and difficulty in CMR volume assessment due to arrhythmia. The remaining 46 patients with heart failure comprised 27 with dilated cardiomyopathy (DCM), 6 with amyloidosis including amyloid light chain and transthyretin amyloidosis, 5 with hypertrophic cardiomyopathy, 2 with drug‐induced cardiomyopathy, 2 with RCM, 1 with ischemic cardiomyopathy, 1 with cardiac sarcoidosis, 1 with left ventricular aneurysm of unknown cause and 1 with left ventricular noncompaction. The clinical characteristics of patients are presented in Table 3.2Thermo, SVFick]) and two methods for estimating ESPs (ESPmPAP and ESPmodified). We investigated the correlation between the estimated RV volume and that determined from CMR imaging.First, we calculated the estimated RV volume using two methods for estimating stroke volumes . Therefore, we adopted this method to estimate EDVs and ESVs using the SVThermo and ESPmodified for further evaluation.As shown in Figure p < 0.0001, Eed: R = 0.80, p < 0.0001).The estimated β and Eed were calculated using EDVs and ESVs, which were determined by the above method. We compared β (CMR) and Eed (CMR) using ESV and EDV obtained from CMR examinations with the estimated β and Eed by our method Figure . Signifi3.3n = 27) and the RCM with the amyloidosis group, which was characterized by marked diastolic dysfunction (n = 8), was performed   between the current method and the method using V0 derived from CMR data  or calculate SV . Furthermore, the use of ESPmodified and SVThermo was correlated more closely with the data exemplified by CMR. The selection of the thermodilution method in SV calculation was consistent with the previous study, which was more reflective of all‐cause mortality than the Fick method  implantation. It has the potential to provide a new risk stratification method for predicting right heart failure, especially for patients with LVAD implantation, by evaluating the right heart function using our method.p < 0.0001), supporting the validity of CMR volumetric evaluation.This study had some limitations. First, the RV volume manually measured by CMR may have some variation. However, CMR is regarded as one of the most reliable methods for evaluating RV volume .EA belongs to the Department, endowed by NIPRO‐Corp, Terumo‐Corp., Senko Medical‐Instrument‐Mfg., Century‐Medical, Inc., ONO‐pharmaceutical‐Co., Ltd. Medtronic‐JAPAN Co., Ltd, Nippon‐Shinyaku Co., Ltd, Mochida Pharmaceutical Co., Boehringer Ingelheim Pharmaceuticals Inc., Abiomed‐Inc, AQuA‐Inc, Fukuda‐Denshi Co., Ltd, and Sun‐Medical‐Technology‐Research Corp. EA received research fund from Bristol‐Myers Squibb Co.Data S1.Click here for additional data file.


Congenital diaphragmatic hernia (CDH) is associated with high neonatal mortality. We performed this study to test the hypothesis that left ventricular (LV) and right ventricular (RV) volumes assessed by three-dimensional echocardiography may be associated with mortality in CDH.This study was a single-center retrospective cohort study involving 35 infants with CDH. RV and LV end-diastolic volume  were measured by three-dimensional echocardiography and were corrected by birth body weight (BBW) on day 1. RVEDV/BBW, LVEDV/BBW, and LVEDV/RVEDV were compared between CDH survivors and non-survivors. Receiver-operating characteristic curve analysis was performed to assess the predictive ability for mortality of the echocardiographic parameters.n = 6) with survivors (n = 29), respectively, RVEDV/BBW was significantly larger , LVEDV/BBW was significantly smaller , and LVEDV/RVEDV was significantly lower . The area under the curve for LVEDV/RVEDV was the largest (0.98).Comparing CDH non-survivors  is high, and evaluating left and right ventricular structures and functions may be helpful in assessing the prognosis.Three-dimensional (3D) echocardiography indicated that the left ventricular end-diastolic volume/right ventricular end-diastolic volume ratio within 24 h after birth was associated with mortality in CDH infants.The usefulness of this ratio should be validated in prospective multicenter studies involving larger numbers of patients. There is also increasing recognition that left ventricular (LV) function may be another key determinant of CDH severity.10 Limited LV dilation capacity enhanced by compression by an enlarged RV and decreased pulmonary venous return owing to PPHN synergistically reduce LV volume and output. Because ventricular volume is determined by loading conditions and ventricular stiffness, and reflects fetal organogenesis and hemodynamics, RV and LV volumes and their balance may reflect the severity in CDH.Congenital diaphragmatic hernia (CDH) is characterized by herniation of the abdominal contents into the thorax. Despite advances in neonatal intensive care and surgical management, CDH continues to cause significant mortality and morbidity.12 with high accuracy and reproducibility, similar to those with CMR.18 Previous studies reported that 3D echocardiography can assess LV and RV volume in newborn infants.20 Accordingly, this study was undertaken to test the hypothesis that LV and RV volumes assessed by 3D echocardiography within the first 24 h after birth are associated with mortality in infants with CDH.Evaluating the volumes of the deformed RV and LV in CDH is difficult using traditional two-dimensional echocardiography because the RV has a complicated shape, and the assumption that the LV is spheroidal does not hold in neonatal CDH. Cardiac magnetic resonance (CMR) imaging, the gold standard measurement of ventricular volume in children and adults, carries a life-threatening risk in CDH, where even moving to the imaging room may exacerbate PPHN. In contrast, three-dimensional (3D) echocardiography can be used at the bedside to determine cardiac chamber volume, independent of angle and without making geometric assumptions,multiple abnormalities, were excluded. Because of the paucity of 3D echocardiography data in this population, a power calculation was not performed.This study was a single-center retrospective cohort study that involved infants with CDH with gestational age ≥36 weeks who were admitted to the neonatal intensive care unit (NICU) within 24 h after birth between January 2017 and June 2021. Infants with significant congenital anomalies, such as cardiac anomalies other than patent foramen ovale, patent ductus arteriosus, and persistent left superior vena cava, as well as 22 CDH cases were managed by a multidisciplinary team in accordance with an institutional treatment protocol, in accordance with Japanese clinical guidelines.23Newborn infants with prenatally diagnosed CDH underwent routine fetal ultrasonography examination. The severity of the condition was quantified by measuring the observed/expected lung-to-head ratio (o/e LHR) and the lung/thorax transverse area ratio during the fetal period.Data on sex, gestational age, birth weight, Apgar scores, and mode of delivery were collected from the electronic medical records. In the CDH group, additional characteristics, side of the defect, treatment, and outcome data were obtained, namely age at repair, stomach and liver positions, cardiovascular therapies, days of age at repair, and survival to neonatal discharge.24 The vasoactive–inotropic score (VIS) at the initial echocardiography was calculated as dopamine dose (mg/kg/min) + dobutamine dose (mg/kg/min) + 100 × epinephrine dose (mg/kg/min) + 100 × norepinephrine dose (mg/kg/min) + 10,000 × vasopressin dose (U/kg/min) + 10 × milrinone dose (mg/kg/min).25 The oxygenation index (OI) at the time of initial echocardiography was calculated using the following formula: (% inspired oxygen × mean airway pressure (mmHg) × 100)/arterial partial pressure of oxygen (mmHg).The respiratory severity score (RSS) at the time of initial echocardiography was calculated as mean airway pressure (mmHg) × fraction of inspired oxygen.Echocardiographic data were collected by a single experienced echocardiographer (K Toyoshima).RV and LV volumes were assessed using 3D echocardiography as part of our institutional protocol. Full-volume 3D echocardiography datasets were acquired by the apical approach using a commercially available ultrasound machine and equipment . The depth and sector angle were adjusted to include the entire RV or LV with the frame rate of >40 frames per second. To encompass the complete RV or LV into the 3D dataset, a full-volume scan was acquired from six R wave-triggered subvolumes. There were six cardiac cycles per capture, which were stitched together. We extracted 3D data from captures of six cardiac cycles with deep sedation, no body motion, and no change in loading conditions.28The 3D echocardiography analysis for LV and RV volume measurements was performed by an experienced investigator (K Toyoshima) using a novel 3D echocardiography software  for which the accuracy and reproducibility have been extensively validated by comparison with CMR.To obtain the LV volume, the LV endocardial border in the LV-focused four-chamber view was semi-automatically determined after two-point clicking of the LV apex and the center of the mitral valve annulus on the apical four‐chamber, two-chamber, and long‐axis views extracted from 3D echocardiography datasets. The endocardial border was manually adjusted, when required. The software generated time domain LV volume curves, from which LV volumes and LV ejection fraction (LVEF) were calculated  (cm3) in the four-chamber view.30 Body size-dependent parameters were divided by the infant’s birth body weight (BBW).We calculated left atrial (LA) volume using the single-plane area–length method with the following equation: LA volume|=|0.85|×|(LA area)To investigate intraobserver variability, 15 studies were randomly selected from the CDH group, with one observer (K Toyoshima) measuring RV and LV volume at 6-month intervals. The observer was blinded to the results of the first measurement. A second observer (H Aoki) independently analyzed these data and was blinded to the results of the first observer. Intra- and inter-observer variabilities were examined by intra-class correlation coefficient (ICC) and Bland–Altman analysis.t test for continuous variables, Mann–Whitney U-test for median values, or Fisher’s exact test for categorical data.Descriptive statistics  were used to summarize the demographic or clinical data of the infants in CDH survivors and non-survivors. Differences between two groups were analyzed using the unpaired 32 Statistical analyses were performed with EZR (version 1.54) , which is a graphical user interface for R  and MedCalc . A P value of <0.05 was considered significant. This study was conducted in accordance with the principles contained in the Declaration of Helsinki and was approved by the institutional review board of Kanagawa Children’s Medical Center .We used univariate logistic regression to predict mortality and calculated the estimated areas under the receiver operating characteristic curves (area under the curve (AUC)) of the models. The optimal cut-off value was determined as the maximum Youden index. We described AUC values of 0.9–1.0, 0.8–0.9, 0.7–0.8, 0.6–0.7, and 0.5–0.6 as excellent, good, fair, poor, and fail, respectively.P = 0.031; Table 1 infusion at echocardiography. No infant received extracorporeal membrane oxygenation.Between January 2017 and June 2021, among 42 infants with CDH who were admitted to our hospital, 35 were included in the analyses  died at a median (range) of 2 (1–42) days of age. Five of the six infants without CDH surgery died 25 (7–34) hours after birth because of marked hypoxia and deterioration despite intensive care  had patent ductus arteriosus at the time of echocardiography. Among the included patients, 19 (54.3%) had a bidirectional shunt, 7 (20%) had a left-to-right dominant shunt, and 3 (8.6%) had a right-to-left dominant shunt. There were no significant differences in the ductal closing or the direction of ductal flow between the survivor and the non-survivor groups (Table Right ventricular function in infants with CDH on day 1 measured by 3D echocardiography was as follows: RVEDV/BBW (ml/kg): 1.98 ± 0.43, RVESV/BBW (ml/kg): 1.21 ± 0.37, RVSV/BBW (ml/kg): 0.74 ± 0.27, RVEF (%): 37.3 ± 9.6, and RV cardiac output (ml/kg/min): 98 ± 39. Left ventricular function in infants with CDH on day 1 measured by 3D echocardiography was as follows: LVEDV/BBW (ml/kg): 1.16 ± 0.34, LVESV/BBW (ml/kg): 0.59 ± 0.19, LVSV/BBW (ml/kg): 0.56 ± 0.24, LVEF (%): 47.5 ± 11.6, and LV cardiac output (ml/kg/min): 72 ± 29. The LVEDV/RVEDV ratio was 0.60 ± 0.21.Table P < 0.001), and smaller LVEDV/BBW  and LVEDV/RVEDV ratio  . Normally, in a given individual, ventricular volume increases in response to an increase in afterload. However, in our CDH patients, RVEDV did not increase as RV Ea increased, and LVEDV and the LVEDV/RVEDV ratio decreased as LV Ea increased , cardiac and respiratory status are not always similarly impaired. The data in this study indicated that the LVEDV/RVEDV ratio is strongly associated with mortality in CDH patients although CDH has been believed to be mainly a respiratory disease. Because pulmonary vessels and parenchyma, and LV size, grow in a developmentally influenced manner, we believe that CDH is a cardiorespiratory disorder. Because postnatal evaluation of pulmonary hypoplasia is difficult during intensive care, 3D echocardiography may provide a useful severity assessment that is related to prognosis in CDH infants.44 The frame rate of >40 frames per second that we used in this study, given the fast heart rate in neonates, may not be ideal, but it is also not low, and the evaluation at this frame rate clearly showed the differences between the groups. With six-beat capture, there may be stitching artifacts with the changes in the loading conditions from the first to the 6th beat. However, the included patients were deeply sedated, and body movements were insignificant. Thus, the effect of the stitching artifacts on the results in this study should be minimal.This is the first study to quantitatively demonstrate, using 3D echocardiography, that the imbalance between LV and RV volumes (the LVEDV/RVEDV ratio) may be useful in assessing CDH severity. However, this study had noteworthy limitations. First, because CDH is a relatively rare disease, the limited sample size in this pilot, single-center study precluded adequate multivariate regression analysis to assess the independence of our main findings from other factors. CDH non-survivors had multiple known risk factors such as lung hypoplasia. Furthermore, ventricular volume is influenced by both intrinsic ventricular stiffness and loading condition, which are in turn influenced by mechanical ventilation, mean airway pressure, drugs, and fluid intake. Multivariate regression analysis is needed to determine whether the 3D echocardiographic data would independently predict the mortality in CDH patients in a future study involving larger numbers of patients. In adults, > 20–25 frames per second is recommended for RV volume measurements.46 while HFO is more likely in Japan.48 How the differences between CMV and HFO affect biventricular volume in CDH patients must be carefully considered. However, this single-center study, performed using a uniform respiratory management policy, showed a marked difference in the LVEDV/RVEDV ratio in CDH survivors and CDH non-survivors. In addition, decreased venous return induced by HFO would affect the LVEDV/RVEDV ratio minimally because a decrease in RV output in turn causes lower LV filling. As another limitation, the single experienced echocardiographer (K Toyoshima) was not blinded to the clinical information of the included patients at the initial 3D data extraction. However, the data extraction processes were semi-automatic, and the intra- and inter-observer variability were acceptable.One may argue that the present results may not be applicable in countries other than Japan owing to differences in the respiratory management strategy. CMV and HFO are the two main ventilatory modes for CDH infants. As an initial ventilatory mode in CDH infants, CMV is often used in Europe and the United States,In conclusion, our 3D echocardiographic data indicated that the volume difference between the RV and LV was remarkable in severe cases of CDH. Thus, the LVEDV/RVEDV ratio may be a useful parameter to reflect CDH severity. Further prospective multicenter studies involving larger numbers of CDH patients are needed to validate the independent clinical usefulness of the 3D LVEDV/RVEDV ratio over traditional echocardiographic parameters.Supplementary Fig. 1Supplementary Fig. 2Supplementary Figure Legends


Extercitatio anatomica de motu cordis et sanguinis in animalibus, where he described “general” circulation, movements and functions of heart, heart valves, veins and arteries History of cardiology starts scientifically in 1628, when William Harvey (1578–1657) published his revolutionary book  The blood was the fundamental vital principle of life with a divine nature. In the Old Babylonian libbu, refers also to the stomach  and libbu were often used interchangeably in the description of emotions kalitu at singular and kalate at plural) are also employed to describe emotions. For instance, the expressions lipassih kalit-ka, lipassih libbi-ka and lipassih habitti-ka, meaning, respectively, “what calms the kidneys”, “what calms the heart” and “what calms the liver” were used for designating a state of calm Many emotional states were described conjugating libbu in relationship to an emotional state, they intended exactly the heart, and not generally the “interior” of the body. At the same time, the fact that only the heart, and not the liver or other organs, was designated with a term characterized by a great richness of meanings indicates that this organ had a special place in the economy of the body. That is, only the heart was indicated with a term equivalent to the interior of the body. This connection might have favoured, in the course of the following cultural history of near civilisations, such as the Egyptian, the Indian and the Chinese ones, the development of the idea that the heart was the spiritual centre of the body, as if the heart became the “interior of the interior of the body”.The fact that also liver and kidneys were connected to emotions might indicate that, when Mesopotamians used the term esu and dalahu, indicated an irregular rhythm of pathologic nature Babylonian Diagnostic Handbook, a “palpitation” of the heart is mentioned in relationship with chest pain, probably in case of myocardial infarction. Interestingly, excess of food and strong emotions were recognized as possible trigger of this condition Mesopotamian doctors were aware that the heart has a rhythmic movement and that the body has at its interior vessels containing blood. Two diagnostic terms, Ghosts could cause heart fluttering and shortness of breath. A prescription mentions juniper and cypress that could have a cardiovascular effect libbu, of diagnostic and therapeutic texts specifically dedicated to the heart, demonstrates that also that organ had an important role. This model might have inspired, or have been connected, with the cardiocentric model developed in other ancient medicines and cultures, such as the Egyptian one.To sum up, even if the liver might have had a prominent role in Mesopotamian medicine and religion, the analysis of the term 2From the Pharaonic Egypt (3000–––332 BCE), we dispose of four manuscripts dedicated to the heart and cardiovascular diseases, contained in the Smith papyrus haty and ib, and three fundamental concepts. 1) Haty, representing cardiac muscle, even if there was no a precise conception of “muscle” Ib or internal-ib, corresponding to the content of thoracic and abdominal cavities, except the heart-haty. In some texts, we find that in the internal-ib of any individual there is a divinity or even that the internal-ib is a divinity itself haty and ib was guaranteed by a network of vessels, named metu (met at singular), which contained all bodily fluids. The heart-ib received sensorial information by sense organs and therefore it was the seat of emotions and intelligence The heart was, at the same time, an anatomic organ and a spiritual symbol. It was characterized by two terms, ibhaty is connected to many expressions related to emotional states, thinking and personal character All the feelings, conditions of the soul, and traits of character were expressed in Egyptian by various idioms referring to the heart, because the compound words included Horus Qâ dating back to the first dynasty (about 3000 BCE). It corresponds to an anatomic illustration extremely precise which has no equal in any other coeval civilization . The “knowledge of the heart’s movement” mentioned in that manuscript, means literally that the heart could move within the body and any change from its proper position was correlated to a pathological condition The interior-ib is weak if the heart-haty does not speak anymore or if the metu of the heart-haty are silent and they don’t give any indication to the hands” In the “Vessel book” or “Book of Heart”, it is written that the heart “speaks” to all the parts of the body through the metu, also the “breath of life” and the “breath of death” were transported The air inspired thought the trachea was the element by which the heart spoke with vessels metu favoured the development of the tactile arterial palpation of the heartbeat by fingertips. Egyptian doctors believed that metu had to be soft and elastic for fulfilling their function and that a state of rigidity might represent a pathological condition. To “measure” radial pulse, it seems that Egyptians used a grain measure specifically calibrated, as can be found in the Smith papyrus The strict relationship between heart and wekhedu (accumulation of by-products of un-expelled bodily waste); heat; excess of blood; something entering from outside; anger; and wrong anatomical positions haty, the metu and the interior-ib, was related to an excess of air in the heart-haty, which, in turn, determined that “physiological” liquids clogged up the metu causing an overflowing affecting the organs of the interior-ibAs for pathological conditions, the heart could be weak because of fever or inflammation of the heart”, the author of the papyrus advances a reasonable advice: “The heart during such disease must be made to rest to some extent if it be possible” In the Ebers papyrus we find a famous description interpreted as referring to a case of angina pectoris Egyptians used a great amount of natural remedies, from plants to minerals, for curing diseases. The use of honey, willow, and sodium is attested in Smith and Ebers papyri, but many other substances were employed, among them also opium poppy as painkiller 3In Vedic medicine , the function of breathing seems to be connected to the health of the heart, preluding yoga techniques which would have developed in India centuries later Hridaya, composed of three roots. Hr-Harana, “to receive”; Da-Dana, “to give away”; and Ayana, indicating the movement and the continuous maintaining of the previous functions Susruta , the heart was defined as a “bud of flower lotus” with the apex facing down  and venous (siras) blood flow was understood Caraka , for instance, the process of tissue nourishment was compared with a rotating wheel The heart was the origin of blood vessels, differentiated as Caraka advanced that for maintaining the health the cardiovascular system, it was necessary to avoid what we would call now as “stress” Vata, Pitta and Kapha, called Dosha  partly resembling Western humoral conception. In the heart, three subtypes of Vata were located: Prana, Vyana and Samana. Then, a subtype of Pitta, the Sadhaka. Finally, a subtype of Kapha, the Avalambaka Ayurveda physiology was based on three principles, Hridaya Roga, they were connected to disorders in diet, mental worries, and to excessive of exercise or, conversely, sedentary habits. This vision seems not far from what contemporary Western medicine has established as risk factors connected to cardiovascular diseases. These features can cause different cardiovascular symptoms that can be summarized in three main categories: pain, dyspnoea and oedema With regard to heart diseases, called In classic Ayurveda texts, about 200 drugs for cardiovascular diseases are mentioned, and among them the most frequent ingredients are Piper longum, Piper nigrum and Zingiber officinale 4The Yellow Emperor’s Inner Canon of Medicine , is stated that the heart, situated in the thorax, had a beat that can be seen or felt under the left nipple, serving as the source of the pulse beat qi, the vital energy of the body and the cosmos, a sort of psycho-physical matter characterized by different degree of thickening.Traditional Chinese Medicine developed from around 2700–2200 BCE to the beginning of the Imperial Unity (dynasty Qin 221–206 BCE). In the qi, in turn, had also the function of pushing the blood all around the body. Indeed, the relationship between heart and lungs was considered fundamental for the functioning of the cardiovascular system The From the heart, three principal conduits originated, connected with kidneys, liver and spleen . Given tqi and air. Transliterated mo, or mai, they are variously translated as “channels”, “vessels”, or “pulse” chin,lo, and sun, interpreted as arteries, veins, and capillaries, but this is a posteriori interpretation, because no proper distinction was made between arteries and veins The vascular system principally consisted in twelve pairs of vessels carrying blood, qi, the blood, and the shen, that is, the spirit or the human mind. Controlling blood, heart governed also body fluids and, with the lungs, transpiration. Armpits and palms were the points where perspiration, correlated also with emotionality, was more abundant, because these parts were crossed by the “heart canal”.Heart is often described as “imperator”, “monarch”, “governor” Qi, blood (xue) and shen were considered, with the jing (essence) and jin yè (bodily fluids), as the five “vital” substances of the human body qi according to different degrees of “thickening”: from the jin yè, the most “material”, to the shen, purely spiritual Qi,shen and jing are called also the “three treasures”, where qi and shen were considered as responsible of the psychic constitution, while the jing was correlated with the physical make-up of the body Shen was responsible of affectivity, thinking, conscience, memory and sleep. If the heart was weak, mental problems could emerge, such as depression, weak memory, sleepiness, insomnia, and loss of consciousness. All emotions affect the heart and the mechanism of the qi. The emotional stress, for instance, causes a stasis of qi that, in turn, determines an excess of heat and fire that, in the long term, dries out the shen, causing anxiety and agitation shen from its natural seat, causing a dilatation of the heart qi, blood and blood vessels is at the base of the complex Chinese theory of “pulses” qi of the heart is strong, blood vessels are in good condition and the pulse is perceived as full and regular. The state of repletion or depletion of blood vessels, could signal illness, and had to be examined at locations in various parts of the body, particularly in the radial pulse. Its study was subdivided in three sectors and five levels of deepness qi” and were fundamental for acupuncture The relationship between heart, qi, blood and blood vessels, emotions and shen, and their circulation in the body could cause a heart disease. Emotions, for instance, were considered the principal “internal” causes of heart diseases. Sadness could exhaust the qi of both heart and lungs, a condition which can be detected with a slow pulse Any disturbance  of Xuanbi antong granule for treating borderline coronary lesion (BCL). In general, for coronary heart disease, traditional Chinese herbal medicine uses Salvia miltiorrhiza, and current studies show that it could relieve small artery circulation, restrain cell apoptosis, and protect the heart against ischemia–reperfusion injury.Finally, among the great number of studies realized in recent years for testing traditional Chinese herbal medicines 5udug, correlated to a heart constriction, the physician was requested to “calm the patient” by using a copper drum, called “hero of heaven”, the noise of which “drives away evil”. A hymn of the Atharvaveda (one of the main texts of Vedic medicine) celebrated the ritual charm as the principal instrument against diseases. Another hymn was dedicated to blood vessels, invoking their state of calm. The Vedic medical men bhisaj, because of dancing and music, was also called shaker and chanter.Due to lack of space, in that paper we did not mention treatment for cardiovascular diseases which included a ritual part based on the recite of incantations and magic formula, often accompanied by drums or music. In a Sumerian incantation against the demon stress response, was well known, as well as that a chronic activation of this survival mechanism impairs health. The American cardiologist Herbert Benson (1935–2022) demonstrated that the human body disposes of a complementary reaction: the relaxation responseMind-Body Medical Institute, renamed Benson-Henry Institute, at Massachusetts General Hospital in Boston, where meditation is regarded as synonymous of relaxation response. We can affirm that even the magical-therapeutic practices of ancient medicines favoured the activation of the relaxation response. Magico-therapeutic rituals were based on repetitive formulas which often have to be recited by both shamans-doctors and patients. In these latter, the recitation might have favoured the concentration of mind, keeping from wandering, as well as a deep and slow breathing.First, these formulas could have been useful in eliciting the placebo effect. By containing statements about their force and effectiveness, they favoured the conviction in the patient to be in the best setting for curing illness. Since the 1970 s, an important physiological reaction has been discovered that can shed further light on the biological efficacy of ancient magical-therapeutic treatments. That the human body, in case of perceived danger, activate the so-called In other terms, it is true that the cardiovascular system was surely not well understood anywhere in antiquity. The heart was not understood as a pump, but remained the center of mind and emotions, since the brain as an organ was also largely misunderstood. However, ancient physicians were aware that we “feel” emotions in our chest rather than in our brains, and that feeling is strictly connected with breathing. Indeed, they developed the idea of a strict connection between mind, emotion, breathing, and heart, which today is at a center of interesting perspectives in neuro-cardiovascular research.Fabio Zampieri: Conceptualization, Investigation, Writing – original draft. Gaetano Thiene: Writing – review & editing. Alberto Zanatta: Validation, Visualization, Writing – review & editing.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


LGE combined with SLE-related organ damage identified patients at high risk of MACE (p < 0.001). In conclusion, the presence, degree, and location of LGE were associated with myocardial dysfunction. The presence, location, and degree of LGE had the potential to independently predict poor prognosis and improve risk stratification in SLE patients.Patients with systemic lupus erythematosus (SLE) typically develop myocardial fibrosis. No studies have investigated the clinical significance of the presence, location, and degree of fibrosis in SLE patients. Seventy-four SLE patients were included. Thirty-seven non-autoimmune disease patients and thirty-seven healthy individuals were included as controls. Myocardial fibrosis was evaluated at cardiac magnetic resonance via a qualitative and quantitative assessment of late gadolinium enhancement (LGE). Myocardial function was measured via speckle-tracking echocardiography. All patients were followed up for the occurrence of major adverse cardiac events (MACE). The presence, locations, and degrees of LGE disturbed regional and global myocardial function. The presence of LGE, left ventricular free-wall LGE (LVFW LGE), and severe LGE were all independent predictors of MACE in SLE patients [LGE presence HR: 3.746 (1.434–9.79),  Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of nuclear autoantibodies, which can cause the inflammatory injury of multiple organs, including all components of the cardiovascular system. Accumulating evidence has shown elevated cardiovascular morbidity and mortality in SLE . MyocardCardiovascular magnetic resonance is a non-radiating technique that is considered the primary imaging modality for myocardial tissue characterization. The application of late gadolinium enhancement (LGE) is currently the most reliable method for the non-invasive detection of focal myocardial fibrosis . LGE hasThe presence of fibrosis is considered to be associated with myocardial dysfunction and poor outcomes in non-ischemic cardiomyopathy ,12. DiffBetween June 2013 and July 2023, a cohort of SLE patients at the Peking Union Medical College Hospital was consecutively enrolled according to the following inclusion criteria: (i) the diagnosis of SLE confirmed according to the American Society of Rheumatology in 1997 ; (ii) paDemographic data, detailed symptoms, the results of laboratory tests, and medical treatments were collected based on medical records. The assessment of SLE-related disease activity (SLE Disease Activity Index 2000 (SLEDAI-2K)) and organ damage  Damage Index (SDI)) was performed on all patients ,17. LaboCardiovascular magnetic resonance images were acquired using a 3.0 T scanner . We obtained cine images via an electrocardiogram-gated two-dimensional balanced steady-state free precession sequence. LGE images were collected 10 min after the injection of 0.1 mmol/kg gadopentetate dimeglumine using a two-dimensional phase-sensitive inversion-recovery gradient-echo pulse sequence. Native and postcontrast T1 mapping was performed using a modified look-locker inversion recovery sequence in a four-chamber long-axis slice and apical, middle, and basal short-axis slices. T2 mapping was acquired using a T2-prepared steady-state free precession sequence. Cardiovascular magnetic resonance images were independently reviewed by experienced investigators who were blind to echocardiographic and clinical outcome data. The visual assessment of LGE was performed according to standardized postprocessing recommendations. The presence of LGE was defined as positive when focal myocardial enhancement was visible in both short-axis and matching long-axis views. Patients with only junctional LGE were classified in the LGE-negative group, as junctional LGE was shown to be nonpathological . The locAll echocardiographic examinations were performed using ultrasound machines GE Vivid 9 . Two-dimensional dynamic images of at least three cardiac cycles from apical four-chamber, three-chamber, two-chamber, and long-axis views were acquired at a frame rate of 50 to 70 frames/second. Atrial and ventricular dimensions alongside volumes were measured according to the American Society of Echocardiography . Apical The clinical endpoint of this study included major adverse cardiac events (MACE), such as cardiac mortality, hospitalization for heart failure, and documented sustained ventricular arrhythmia (>30 s). All patients were followed up every 3–6 months on the telephone using the standard questionnaire interview and clinical medical records. The time until the endpoint was calculated from the date of the baseline cardiovascular magnetic resonance examination. The data of all patients were included up to the last date of follow-up.t-test or Mann–Whitney rank sum test, or chi-square test. Comparisons across 3 groups were performed using a one-way analysis of variance (ANOVA) or the Kruskal–Wallis test. Event-free survival was assessed using Kaplan–Meier analyses, with comparisons performed via the log-rank test. Univariate and multivariate Cox proportional hazard analyses were adopted to identify the predictors associated with prognosis. Initial univariate analyses were performed based on the primary parameters of interest, including clinical and imaging parameters. Subsequently, the variables with p < 0.05 in univariate analysis, as well as age, sex, and cTnI, were included in multivariate analysis. Repeated measurements of functional parameters were performed on 20 randomly selected participants. The intraclass correlation coefficient was applied for the assessment of intra-observer and inter-observer reliability. All statistical analyses were processed using a standard statistical software program . A p-value < 0.05 was considered statistically significant.Continuous variables were expressed as the mean ± standard deviation (SD) or median with an interquartile range (IQR) based on a normal or skewed distribution. Categorical variables were presented as the frequency and percentages. Comparisons between 2 groups were carried out using the independent samples n = 5), ischemic coronary disease (n = 1), severe valvular disease (n = 6), more than 1 month between cardiovascular magnetic resonance and echocardiography (n = 5), and poor image quality (n = 18). Finally, 74 patients were enrolled in this study . In the context of comparable SLE-related disease activity and cumulative organ damage levels, SLE patients with LGE had serious cardiac symptoms and myocardial injury compared to those without LGE. SLE patients with LGE had a higher incidence of antiphospholipid syndrome than those without LGE. The global myocardial function was significantly impaired in all SLE patients regardless of the presence or absence of LGE when compared with the healthy controls . Meanwhile, SLE patients with LGE presented with lower global WE (GWE) than those without LGE .Among the included 74 SLE patients, 39 (52.7%) developed LGE. The incidence of LGE in patients with SLE and patients with non-autoimmune diseases was comparable . In patients with non-autoimmune disease-related cardiomyopathy, LGE is most often located in both the septum and free wall , followed by only the septum . Comparisons between patients with (n = 19) and without left ventricular free-wall (LVFW) LGE (n = 55) showed no significant difference in age, gender, and SLE disease activity (n = 20) and LVFW-only LGE (n = 9) demonstrated that patients with LVFW-only LGE had higher global PSD when fibrosis degrees were comparable  cases, only in the left ventricular free wall in 9 (12%) cases, and in both locations in 10 (14%) cases. There was a difference in the location of LGE between patients with SLE and non-autoimmune diseases  (Patients with SLE had a comparable degree of LGE to patients with non-autoimmune disease-related cardiomyopathy [median (IQR): 1.74% (0%–3.84%) vs. 2.9% (0.8%–4.95%), = 0.021) .All intraclass correlation coefficient values of GLS, PSD, GWE, global WI, global CW, and global WW were greater than 0.75, which indicated good intra-observer and inter-observer repeatability .p = 0.058).Over a median follow-up of 25.5 (IQR 17-48.5) months, 32 MACEs occurred in 27 (36%) patients as follows: 11 (15%) cardiac deaths, 19 (26%) heart failure hospitalizations, and 2 (3%) cases of sustained ventricular arrhythmia. The incidence of MACE tended to be higher in patients with SLE compared to those with non-autoimmune diseases . Meanwhile, SLE patients with LGE had a higher incidence of MACE than those without LGE (log-rank p = 0.008) (p = 0.012) (p = 0.007)  A. The un= 0.012) . In the = 0.007) .p = 0.027) (p = 0.023) (p = 0.044) and cardiac mortality   B. Univar= 0.023) . The mul= 0.007) .p = 0.007)   C. The un= 0.019) .p < 0.01)  .In this retrospective study, we combined cardiovascular magnetic resonance and speckle-tracking echocardiography to evaluate myocardial injury in SLE patients. To our knowledge, this is the first study to examine the association between the presence, locations, and degrees of LGE and regional/global myocardial function and analyze their prognostic value in SLE patients. The main findings are as follows : First, Myocardial fibrosis is a histopathological remodeling process characterized by excessive accumulation in the myocardium of extracellular matrix components in response to an injury. LGE measured via cardiovascular magnetic resonance is a sensitive tool and a first-line non-invasive exam to detect myocardial fibrosis . In our In recent years, several clinical studies have focused on the association between myocardial fibrosis and myocardial function. Patients with myocardial fibrosis have been discovered to manifest global myocardial dysfunction . Some stBoth LVEF and GLS are considered standard parameters for left ventricular quantification in guideline recommendations. However, both GLS and LVEF are susceptible to changes in preload and afterload, leading to the misinterpretation of the true systolic function of the myocardium. Since myocardial work incorporates both the strain and afterload simultaneously to reduce load dependence, myocardial work adds incremental value to the existing evaluation of the intrinsic myocardial function . Our stuPrevious studies have shown that LGE is associated with an increased risk of adverse cardiac outcomes in non-ischemic cardiomyopathy ,29. MeanRecent studies have identified the association between the location of LGE and clinical prognosis. Similar to this study, some studies showed that fibrosis located in the left ventricular free wall impacted the prognosis of the disease. A multicenter study of left ventricular noncompaction revealed that LVFW LGE was associated with an increased risk of MACE . A cohorThe clinical significance of the degree of fibrosis in myocardial disease has also been the focus of recent studies of non-ischemic cardiomyopathy. The degree of LGE was found to be mainly associated with all-cause mortality  and MACEThe SDI has been widely utilized to assess cumulative organ damage in SLE. The SDI includes non-reversible changes in organs affected by the process of disease process. Our data showed that the SDI was an independent predictor of poor cardiac prognosis in SLE patients. Furthermore, patients with both cumulative organ damage and myocardial fibrosis had the highest risk of MACE. The results highlight that the combination of myocardial fibrosis and SLE-related systemic organ damage was conducive to identifying SLE patients at high risk for adverse clinical outcomes. Myocardial fibrosis had the potential to enhance the risk assessment and stratification of SLE patients.Our study has several limitations. First, it was a single-center observational study with a limited cohort of SLE patients. However, the sample size in our research compared favorably with some previously published studies about myocardial injury by cardiovascular magnetic resonance in SLE . Second,In SLE patients, focal fibrosis with different characteristics disturbed regional and global myocardial dysfunction. Their presence, location, and degree were independent predictors of poor prognosis in patients with SLE. Myocardial fibrosis combined with SLE-related organ damage helped to improve the cardiac-related risk stratification of SLE patients. The prevention and treatment of myocardial fibrosis need to be the focus of future research to improve the myocardial function and clinical prognosis of SLE patients.


Studies suggest that different software tools cannot be used interchangeably in humans. In this study, we sought to compare the left ventricular parameters in gated 18F-FDG imaging using a small-animal nanoPET/CT (Mediso) under isoflurane narcosis. Reconstructed gates PET images were subsequently analyzed in three different software tools, and cardiac volume and function (end-diastolic (EDV), end-systolic volumes (ESV), stroke volume (SV), and ejection fraction (EF)) were evaluated. While cardiac volumes correlated well between PMOD, MIM, and QGS, the left ventricular parameters and cardiac function differed in agreement using Bland–Altman analysis. EDV in PMOD vs. QGS: r = 0.85; p < 0.001, MIM vs. QGS: r = 0.92; p < 0.001, and MIM vs. PMOD: r = 0.88; p < 0.001, showed good correlations. Correlation was also found in ESV: PMOD vs. QGS: r = 0.48; p = 0.07, MIM vs QGS: r = 0.79; p < 0.001, and MIM vs. PMOD: r = 0.69; p < 0.01. SV showed good correlations in: PMOD vs. QGS: r = 0.73; p < 0.01, MIM vs. QGS: r = 0.86; p < 0.001, and MIM vs. PMOD: r = 0.92; p < 0.001. However, EF among correlated poorly: PMOD vs. QGS: r = −0.31; p = 0.26, MIM vs. QGS: r = 0.48; p = 0.07, and MIM vs. PMOD: r = 0.23; p = 0.41. Inter-class and intra-class correlation coefficient were > 0.9 underlining repeatability in using PMOD, MIM, and QGS for cardiac volume and function assessment.Healthy mice underwent ECG-gated 18F-FDG PET/CT imaging. However, due to software-related differences in agreement analysis for cardiac volumes and function, PMOD, MIM, and QGS cannot be used interchangeably in murine research.All three commercially available software tools are feasible in small animal cardiac volume assessment in gated The online version contains supplementary material available at 10.1186/s13550-023-01026-w. Many software tools have been developed and are essential for the clinical and preclinical analysis of single photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging.The commercially available software covers various research areas, including oncology –3, neuro177Lu-DOTATATE [82Rubidium PET myocardial perfusion quantification in patients was recently used to validate the novel Carimas software [13N-ammonia PET for myocardial perfusion. This study showed consistent global and regional myocardial blood flow (MBF) values. However, there was significant variability in segmental values supplied by the circumflex branch of the left coronary artery. These differences limit the interchangeability of the studied software tools [However, comparing software applications is still challenging and can result in different dosimetry analyses of clinical data derived from peptide receptor radionuclide therapy (PRRT) using DOTATATE . For oveDOTATATE . HoweverDOTATATE . 82Rubidsoftware . Cross-cre tools . Anotherre tools .13N-ammonia PET and the respective vascular territories [82rubidium imaging quantification depended on software tools  [Comparison of QPET, syngo MBF, and PMOD resulted in excellent correlations in myocardial flow reserve (MFR) in ritories . Howeverngo MBF) .18F-FDG represents a widely used tracer detecting hibernating myocardium [18F-FDG tracer can also be utilized in small animal PET research for the detection of myocardial defects and to assess murine heart function [Gated data acquisition in myocardial perfusion SPECT and PET allows analysis of wall motion and calculation of left ventricular volumes, including end-diastolic (EDV), end-systolic volumes (ESV), and left ventricular ejection fraction (EF). Left ventricular cardiac volumes and EF are reliable prognostic parameters in patients . In the ocardium , 21, proocardium , 23, andocardium , 25. Preocardium , 27. Sevfunction –30.To date, no studies are comparing different software tools for cardiac volumes and function in basic murine research.18F-FDG PET/CT imaging, thereby contributing to the existing literature on its feasibility and differences and assessing interchangeability.In this study, we sought to compare the left ventricular parameters using PMOD, MIM, and QGS in cardiac small animal Male C57/Bl6J mice were purchased from Charles River Laboratories . In total, 15 healthy mice, 8 male and 7 female, at 8 weeks of age were used. Mice's heart rate was 492 ± 53 beats per minute.Animal care and all experimental procedures were performed according to the Guideline for the Care and Use of Laboratory Animals published by the US National Institutes of Health . Study protocols complied with the institution's guidelines and were approved by the Government's animal ethics committee.18F-FDG-PET/CT scans were performed using a small-animal PET/CT scanner . The animals had free access to food and water until before the scan, as described previously [ECG-gated eviously –32. No pAnesthesia was induced (2.5%) and maintained (2.0%) with isoflurane delivered in pure oxygen at a rate of 1.5 L/min via a face mask. The core body temperature was maintained within the normal range using a heating pad and monitored by a rectal thermometer.18F-FDG was injected in a volume of ~ 0.1 ml. The catheter was then flushed with 0.05 ml of isotonic saline solution. Animals remained anesthetized during the entire scan and were placed in a prone position within the PET/CT scanner.After placing an intravenous catheter into a tail vein, approximately 20 MBq of Modified neonatal needle ECG electrodes  were placed into both forepaws and the left hind paw. An integrated physiological monitoring system recorded the ECG signal and vital parameters.First, a CT scan  was acquired for attenuation correction. The ECG-gated PET recording was initiated 30 min after the tracer injection and lasted 15 min. Recovery from anesthesia and the PET/CT scan was monitored closely by a veterinarian. Gated mouse PET studies were reconstructed using the Tera-Tomo 3-dimensional reconstruction algorithm , which includes point-spread correction and the following settings: 8 iterations, 6 subsets, normal regularization, median and spike filter on, edge artifact reduction on, voxel size of 0.5 mm, and 400- to 600- keV energy window, and coincidence mode 1–3. Gating parameters were set at 16 frames. All PET data were corrected for randoms, scatter, attenuation, and decay.Gated mouse PET images were processed as described previously . AnalysiReconstructed whole body PET files were imported into PMOD . An automated protocol for mice was used for gated image analysis. PMOD automatically converts the ECG-gated files into dynamic PET images. Endocardial and epicardial contours were automatically traced in the PET images. Based on the contours, various parameters of the left ventricle were calculated: EDV, ESV, SV, and EF.MIM (Version 7.1.11) was used for image registration and atlas-based segmentation to generate left ventricular myocardial contours. Gated whole-body PET images were adjusted by a scaling factor using the Python script to enable analysis in the automated cardiac PET mouse workflow provided by the company.After manually adjusting the heart’s orientation , an automated registration is performed to match the heart registration and define the contours. Left ventricular parameters  were automatically calculated.U test, was applied for groups without normal distribution. EDV, ESV, SV, and EF were analyzed using matched one-way ANOVA with Sidaks multiple comparison test. The correlation was calculated using Pearson correlation coefficients between two datasets; scatter diagrams and Bland–Altman plots showing difference vs. average were used for visualization and further analysis of bias and agreement. To assess the intra- and inter-reader reproducibility, cardiac volume assessment in all three software applications were repeated 10 weeks after the initial review by the same reviewer and by a second reviewer, for the calculation of intraclass correlations coefficients (ICCs) with 95% confidence intervals (CI). The studies were presented in a random order. Differences were considered statistically significant at a p-value of 0.05.All results are reported as mean ± standard deviation (SD). Statistical analysis was performed with Prism  and IBM SPSS Statistics (Version 29.0.0.0 (241)). No outlier correction was performed in the dataset. The Wilcoxon signed rank, or the Mann–Whitney 18F-FDG PET images could be analyzed using all three commercially available software packages. Figure p < 0.05) and PMOD vs. MIM (p < 0.01) differed significantly, while QGS vs. MIM showed similar results (p = n.s.). ESV was different among all three software applications (p < 0.01). Regarding the SV, QGS differed significantly from PMOD (p < 0.001) and MIM (p < 0.001). SV among PMOD and MIM resulted in similar results (n.s.). Interestingly the EF in QGS was consistently higher compared to PMOD (p < 0.001) and compared to MIM (p < 0.001). However, PMOD vs. MIM also showed differences in EF (p < 0.01). The mean values, including standard deviation and range for EDV, ESV, SV, and EF, are displayed in Table Gated mouse p < 0.05). Other cardiac volumes such as ESV, SV, and EF did not differ  from patients were measured by commercially available pharmacokinetic software packages  . HoweverThe reader should be aware of several limitations in this study. First, our data lack a non-PET imaging external reference control such as magnetic resonance imaging or echocardiography. Second, the number of comparable studies in small animals is minimal, underlining the need for further investigation. Third, potential errors and artifacts in automated processing cannot be excluded since QGS and MIM were programmed for humans, not small animals. That could attribute to high spillover fractions in imaging small mice hearts. Although this study analyzed different software tools, the data was obtained with one scanner and one imaging and reconstruction protocol. Forth, only intravenous FDG application into a tail vein was performed. Intraperitoneal injection was not performed but could represent benefit by avoiding prolongation of isoflurane anesthesia, which may mask efficacy of glucose suppression.18F-FDG PET/CT. Our results indicate that these software tools are feasible in small animal research. The calculated cardiac values are consistent with the published literature. There was a good to excellent correlation for EDV, ESV, and SV comparing the software tools. Bland–Altman analysis showed differences in agreement, limiting the interchangeability of PMOD, MIM, and QGS for murine cardiac volume and function assessment.Analyzing heart volume and function in small animal research is a cornerstone in preclinical cardiac research. Regarding the previous lack of published literature, the present work compares three commercially available software tools for cardiac function in healthy mice using gated Additional file 1: Comparison of cardiac PET parameters by gender: male vs. female for EDV (A), ESV (B), SV (C), and EF (D) using QGS (in black), PMOD (in grey), and MIM (in white). The left y-axis depicts volume assessment in µl (A to C); y axis in (D) shows the EF in %. Male mice N=8, female mice N=7. Data represents mean ± SD. *p < 0.05, **p < 0.01, ***p < 0.001.


Ejection fraction (EF), which is assessed using ultrasonography, is a standard parameter for evaluating cardiac function in clinical cardiology and for cardiovascular management during general anesthesia. However, it is impossible to continuously and non-invasively assess EF using ultrasonography. The aim of our study was to develop a method for estimating EF non-invasively using the left ventricular arterial coupling ratio (Ees/Ea).Ees/Ea was estimated non-invasively using the parameters pre-ejection period (PEP), ejection time (ET), end-systolic pressure (Pes) and diastolic pressure (Pad), which were calculated from a vascular screening system, VeSera 1000/1500 . Then, left ventricular efficiency (Eff) as a pump, defined as the ratio of external work (EW) to myocardial oxygen consumption, which strongly correlates with the pressure-volume area (PVA), was calculated by a new formula using Ees/Ea, and was used to approximate EF (EFeff). Simultaneously, we measured EF using transthoracic echocardiography (EFecho), and compared it with EFeff.2 = 0.219, p < 0.05) on Bland-Altman analysis, with limits of agreement of – 7.5 to 24.4%, and percentage error of 24%.The study included 44 healthy adults , in whom mean EFecho was 66 ± 5% and EFeff was 57 ± 9%. We found a positive correlation between EFecho and EFeff (RThe results suggest that EF can be measured non-invasively using left ventricular arterial coupling. Measurement of ejection fraction (EF) by transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) is a standard method for evaluating cardiac function. EF and wall motion calculated from TEE are useful during separation from cardiopulmonary bypass and understanding circulatory dynamics during cardiac surgery , and forLeft ventricular arterial coupling (Ees/Ea), which is the ratio of end-systolic elastance (Ees) to effective arterial elastance (Ea), expresses the relationship between left ventricular pump function and systemic vascular resistance . In a prThe aim of our study was to develop a method to estimate EF noninvasively from Ees/Ea.The protocol of this prospective, observational study was approved by the Research Ethics Committee of the University of Fukui Hospital  and the study was conducted in accordance with the Declaration of Helsinki. Informed consent was obtained from all participants and/or their legal guardian(s). Forty-four healthy volunteers were evaluated between 2018 and 2020, after excluding subjects with cardiovascular diseases. Their age, sex, height and weight were recorded.In all the subjects, transthoracic echocardiography was performed using a Vivid E9 ultrasound  in the left lateral position. EF was obtained by the modified Simpson’s method, and stroke volume (SV) was estimated by subtracting left ventricular end-systolic volume (ESV) from the end-diastolic volume (EDV).After transthoracic echocardiography, the cardio-ankle vascular index (CAVI) was determined using a vascular screening system, VeSera 1000/1500  with the participant in the supine position. A standard four-lead ECG and stethoscope were attached to the subject’s chest, and four blood pressure cuffs were attached around the arms and ankles. ECG, phonocardiogram, and brachial arterial pulse waves were continuously recorded. Pre-ejection period (PEP), ejection time (ET), systolic blood pressure (sBP), and diastolic blood pressure (dBP) were automatically recorded.ET was defined as the interval between the start of the upstroke and the direct notch of the right brachial arterial pulse wave. PEP was calculated by subtracting ET from the time between the Q wave on the ECG and the second heart sound. sBP and dBP were measured using the blood pressure cuffs. End-systolic pressure (Pes) was calculated from sBP and dBP using Kappus et al’s formula , as:Additionally, the left ventricular pressure-volume loop, which is a curve used to plot left ventricular volume and left ventricular pressure and is used to understand cardiac mechanics, was plotted using TTE parameters . Left veEes represents the slope of the end-systolic pressure volume relationship (ESPVR), and is an index of left ventricular contractile ability . It is cIn a previous study, Hayashi et al. found that Ees/Ea can be estimated by a noninvasive method using four parameters, pre-ejection period (PEP), ejection time (ET), end-systolic pressure (Pes), and diastolic blood pressure (dBP)  Fig. 1BB1B. SincHere, E(t) was expressed as the change in elastance of the left ventricle on standing. The ratio of the slope when E(t) was approximated bilinearly in the isovolumic contraction phase and the isovolumic ejection phase was defined as k. The hypothetical Pmax that would develop if the aorta was clamped was expressed using PEP, ET, and Pad as:In addition, when the increase in left ventricular pressure from Pes to Pmax and the increase in aortic pressure to Pes occur with the same ejection volume, the ratio of Ees to Ea can be expressed asRearranging Eqs. Based on this theoretical formula and experiment,Ees/Ea was calculated by simultaneously solving Eqs. Left ventricular efficiency (Eff) as a pump is defined as the ratio of external work (EW) to myocardial oxygen consumption, and strongly correlates with the pressure-volume area (PVA), as indicated by the pressure-volume loop  Fig. 1AA1A. In tRearranging Eqs. EF is the ratio of SV to left ventricular EDV.Assuming V0 is zero, using Eqs. SPSS was used for the statistical analysis. The sample size of subjects required in this study to produce an α = 0.05 and a power of 0.80 was adopted from a previous study . The samEFecho and EFeff were compared using simple regression analysis and Pearson’s correlation analysis. Additionally, Bland-Altman analysis was used to assess agreement between the two . EF measThe agreement between EFecho and EFeff was interpreted as acceptable when the PE was ≤ 30% . Signifi2 = 0.219, P < 0.05) . The characteristics of the participants are shown in Table Bland-Altman analysis showed a bias of 8.5 ± 8.0%, with limits of agreement of − 7.5–24.4%. The PE was 24% . It is difficult to calculate EF continuously from TTE. Additionally, TEE  is highly invasive and might be associated with complications, such as odynophagia, upper gastrointestinal hemorrhage, and esophageal perforation . It is, EF is expressed by the ratio of SV to Ved, as in Eq. In this study, CAVI was performed in the supine position, whereas TTE was performed in the left lateral position. This is because it is easier to apparatus the apex of the left ventricle in the supine position allowing more accurate calculation of EDV.Although SV was measured by TTE in the present study, it is impossible to perform TTE continuously during surgery. Stroke volume and arterial pressure-based cardiac output, which is the cardiac output obtained using an arterial pressure waveform, can be obtained using a Flotrac hemodynamic monitoring system  . Our futThere are several limitations in the present study. First, all of the study participants were young, healthy people with no cardiac diseases. On the other hand, since patients with cardiac disease occasionally have abnormal heart rhythms and might develop irregular Q waves, the values of PEP and ET cannot be accurately calculated. However, since the purpose of this study was to examine a method of calculating EF using left ventricular arterial coupling in persons with normal cardiac function, we decided to only include healthy participants in this study. In future, it will be necessary to examine whether it is possible to calculate EF using left ventricular arterial coupling in people with cardiac diseases, with similar correlation and agreement. Second, in this study, we assumed that V0 was 0 ml, which was only possible because the study included participants with normal cardiac function .In conclusion, the results of the present study suggest that EF can be monitored noninvasively and continuously using the parameter of left ventricular arterial coupling.


Acute dyspnea (AD) is one of the main reasons for admission to the Emergency Department (ED). In the last years integrated ultrasound examination (IUE) of lung, heart and inferior vena cava (IVC) has become an extension of clinical examination for a fast differential diagnosis. The aim of present study is to assess the feasibility and diagnostic accuracy of E/A ratio for diagnosing acute heart failure (aHF) in patients with acute dyspnea. We included 92 patients presenting to the ED of CTO Hospital in Naples  for AD. All patients underwent IUE of lung-heart-IVC with a portable ultrasound device. Left ventricle diastolic function was assessed using pulse wave doppler at the tips of the mitral valve and E wave velocity and E/A ratio were recorded. The FINAL diagnosis was determined by two expert reviewers: acute HF or non-acute HF (non-aHF). We used 2 × 2 contingency tables to analyze sensitivity, specificity, positive predictive and negative predictive value of ultrasound parameters for the diagnosis of AD, comparing with the FINAL diagnosis. Lung ultrasound (LUS) showed high sensitivity, good specificity and accuracy in identification of patients with aHF. However, the highest accuracy was obtained by diastolic function parameters. The E/A ratio showed the highest diagnostic performance with an AUC for aHF of 0.93. In patients presenting with AD, E/A ratio is easy to obtain in a fast ultrasound protocol and showed an excellent accuracy for diagnosis of aHF. Initial assessment of patients with acute dyspnea is commonly based on medical history, physical examination, chest X-ray, 12-lead electrocardiogram, arterial blood gas analysis and routine blood tests [In the last years, integrated ultrasound examination (IUE) of lung, heart and inferior vena cava become an extension of clinical examination for a fast assessment of acute dyspnea in emergency setting –4.Lung ultrasound (LUS) is widely demonstrated to be superior for the identification and evaluation of extravascular lung water when compared to chest X-ray –7. The iWe have recently demonstrated that the combination of positive LUS with FoCUS, including dilated left atrium and reduced ejection fraction, substantially extends the spectrum of recognizable aHF .Left ventricle (LV) diastolic dysfunction represents the main pathophysiological abnormalities in HF as it plays an important role in determining increased LV filling pressures with consequent development of venous congestion and pulmonary edema. Its assessment in the context of emergency department is feasible and may help to improve rapid diagnostic assessment of patients with acute dyspnea .The aim of the present study is to assess feasibility and diagnostic accuracy of simple parameter of diastolic function assessment (E wave velocity and E/A ratio) included in a fast protocol of IUE for diagnosing aHF in patients with undifferentiated dyspnea in emergency department.From January 2019 to June 2019, we enrolled 113 patients presenting to the emergency department of CTO Hospital in Naples  for acute dyspnea or sudden worsening of chronic dyspnea within the previous 48 h. Patients with dyspnea of traumatic origin were excluded. 21 patients with atrial fibrillation (AF) were excluded from the study; thus, the final study population included 92 patients. Patients were enrolled consecutively during the shift of the involved physicians in the study. All patients underwent clinical examination, blood gas analysis, chest X-ray, ECG, and routine blood tests (including BNP). BNP was considered negative if < 100 pg/mL according to current guidelines on HF . Chest Xt-test, while chi-square distribution was used to compare categorical variables. A p-value < 0.05 was considered statistically significant. The population was divided into two groups: patients with aHF and patients without acute HF (non-aHF). The performance of each different diagnostic tests for the diagnosis of aHF  was analyzed, and comparisons were made among them, using sensitivity, specificity, positive predictive value, negative predictive value. Confidence intervals (CI) at 95% were calculated for sensitivity, specificity, positive predictive value, and negative predictive value. Areas under the curve (AUC) and receiver operating characteristic (ROC) curve were used to compare the performance of each different ultrasound diagnostic tests in relation to the final diagnosis [. Yuoden index was used to calculate the optimal threshold value (cut-off point) for E/A ratio to identify patients with acute HF. A combined clinical score was built to assess the diagnostic accuracy of E/A ratio on top of common clinical characteristics of the patients including anamnestic history, chest X ray, BNP value and dilated LA. We estimated probability of having aHF as final diagnosis using a multivariable logistic regression model including anamnestic history, chest X ray, BNP value and dilated LA. Then, in a second model, E/A ratio was also added. For each model, individual risk estimates were based on the sum of weighted scores for each variable and compared using receiving operating characteristic curves, and the areas under the curve (AUC) were calculated. Detection of a significant difference between two AUC indicates significant difference in the overall ability of the prediction with the largest area indicating the best predictive model. The method of Delong et al [The ultrasound examination was done within 30 min from the arrival of the patients in ED. Two emergency physicians performed all the ultrasound examinations. The final diagnosis, considered as the gold standard, was issued by two independent observers who had access to the entire medical chart  of each patient . Based on this revision, patients were classified into two groups: aHF or non-cardiac dyspnea (non-aHF). Acute HF was defined according to current guidelines . In patiiagnosis . Yuoden ng et al  for the p < 0.05). Patients with acute HF had more frequent medical history of heart failure and or ischemic heart disease. Table Our study population included 92 patients 25 patients (27%) had aHF, and 67 patients 73%) had non-cardiac dyspnea (non-AHF). Number of patients with HFrEF was 13, first episode of HF was diagnosed in 13 patients. Table % had nonp < 0.05). LUS positivity for bilateral IS and/or effusion exhibited high sensitivity (80%), good specificity (70%) and accuracy (76.11%) for the diagnosis of aHF. Dilated left atrium showed the highest sensibility in identifying aHF (96%). In an additional analysis we calculate, through the Yuoden Index, the best cut-off value for E/A ratio to identify acute HF. The Youden Index value for E/A ratio was 0.95. Table p < 0.05).Table p = 0.03). A second ROC curve analysis was built comparing accuracy of E/A ratio with BNP level as continuous variable and is reported in Fig. p = 0.69).Roc curve analysis were built to assess diagnostic accuracy of different modalities. Figure p < 0.02).Multivariate regression models to predict aHF were built including anamnestic history of heart failure/ ischemic heart disease, chest X-ray, BNP value and dilated LA as model 1. Then, E/A > 0.95 was added in model 2. Figure The present study demonstrated that the evaluation of E/A ratio in a fast-integrated ultrasound protocol has an excellent accuracy for diagnosis of acute HF in patients presented to the ED with acute dyspnea. E/A ratio is easy to obtain within a 3-min fast ultrasound protocol allowing the identification of patients with acute HF. Our results demonstrated that E/A ratio used on top of clinical examination including anamnestic history, chest X-ray, BNP value and dilated LA significantly improves accuracy in detection of acute HF as a cause of acute dyspnea. Our results strongly encourage the use of E/A ratio as an easy and rapid tool for the diagnosis of HF.The diagnosis of HF in patients presenting to the ED with acute dyspnea remains challenging. It was demonstrated the utility of integrated heart and lung ultrasound examination for an ultrafast diagnosis of HF in the emergency setting , 3. The FoCUS identifies cardiac abnormalities and can help to explain the acute onset of HF. Diastolic dysfunction of the left ventricle is presented in all types of HF, regardless of the value of EF. It represents a combination of impaired LV relaxation, restoration forces, myocyte lengthening load, and atrial function, culminating in increased LV filling pressures with congestion or pulmonary edema and left atrial dilation . We haveCurrent Doppler echocardiography guidelines recommend using early to late diastolic transmitral flow velocity (E/A) to assess diastolic function, and E to early diastolic mitral annular tissue velocity (E/e’) to estimate LV filling pressures . UnfortuAs reported in Table In this study, the operator was experienced in both FoCUS and LUS. It was demonstrated that emergency physicians were able to perform and interpret focused echocardiography reliably after a short duration of training , 34.Our study has some limitations. First, the population sample is limited. A larger study population is needed to confirm our results and the tendency of E/A ratio to be statistically more significant than dilated left atrium. It should be underlined that different pathophysiological conditions such as severe mitral annular calcification, severe valvular diseases, stimulated pacemaker rhythm, tachycardia or severe anemia might have impact accuracy of diastolic dysfunction evaluated by E/A ratio. Also, full assessment of diastolic dysfunction is not always feasible and as demonstrated in our study, even simple E/A ratio was not available in about 20% of the study participant . The opeIntegrated ultrasound examination is a useful tool for differential diagnosis in patients admitted to the ED with acute dyspnea. In all types of heart failures regardless of ejection fraction, the left ventricle diastolic dysfunction plays an important role in congestion or pulmonary edema and consequent respiratory symptoms. E/A ratio showed an excellent diagnostic accuracy in diagnosing acute HF when assessed in ultrafast ultrasound protocol.