Background: Collaboration between cardiac surgeons and cardiologists can offer interventions that each specialist may not be able to offer on their own. This type of collaboration has been demonstrated with the hybrid Stage I in patients with hypoplastic heart syndrome. Since that time, a hybrid approach to cardiac interventions has been expanded to an incredible variety of potential indications.Methods: Seventy-one patients were scheduled for a hybrid procedure along 8 years. This was defined as close collaboration between surgeon and cardiologist working together in the same room, either cath-lab (27 patients) or theater (44 patients).Results: Six groups were arbitrarily defined. A: vascular cut-down in the cath-lab (27 neonates); B: bilateral banding  in hypoplastic left heart syndrome or alike (15 children); C: perventricular closure of muscular ventricular septal defect (10 cases); D: balloon/stenting of pulmonary branches along with major surgical procedure (12 kids); E: surgical implantation of Melody valve (six patients) and others . Two complications were recorded: left ventricular free wall puncture and previous conduit tearing. Both drawbacks were successfully sort out under cardiopulmonary by-pass.Conclusion: Surgeon and cardiologist partnership can succeed where their isolated endeavors are not enough. Hybrid procedures keep on spreading, overcoming initial expectations. As a bridge to biventricular repair or transplant, bilateral banding plus ductal stent sounds interesting. Novel indications can be classified into different groups. Hybrid procedures are not complication-free. Surgical and percutaneous procedures have experienced striking advances in congenital heart diseases along the past decades. Collaboration between interventional cardiologists and cardiac surgeons has recently paved the way for the so-called “Hybrid procedures”. In offering a hand-to-hand intervention, the result becomes less invasive and more efficient, rendering a safer management for the congenital condition.Partnership in the field of aortic valve replacement in the adult population  is an example of hybrid approach. The first report of a hybrid procedure  in a neoThis holds true not only for the hypoplastic left heart pathway but also for a vast array of cardiac conditions in which surgical or percutaneous procedures in isolation cannot address the problem. As this field keeps on growing, more sophisticated hybrid rooms will be devised to cope with the increasing needs of both surgeons and cardiologists.Our group experience along eight consecutive years is presented. Provided the sparking use and indications for hybrid procedures, we intend to cluster them into several categories. The rationale for assignment to cath-lab or theater will be discussed and the complications analyzed.From January 2013 until December 2020, 71 patients underwent a hybrid procedure to treat their cardiac condition in our Institution. The studies involving human participants were reviewed and approved by Hospital Gregorio Marañón's ethics committee. The patients/participants parents provided written informed consent to participate in this study. Data are recorded in a prospective manner. According to underlying disease and main procedure accomplished, they have been arbitrarily divided into groups :A. Cut-down vascular access (27 patients)B. Hypoplastic left heart syndrome or alike (15 children)C. Perventricular ventricular septal defect closure (10 cases)D. Pulmonary artery branches dilatation/stenting E. Biological valve (Melody) deployment in open-heart field (6 patients)F. Others (one case).The decision to carry out the hybrid procedure in the cath-lab or in surgical theater was based upon the likelihood of cardiopulmonary by-pass needs (performed in theater). Cath-lab and theater are located in the same level, with a corridor in between both suites. Transition from cath-lab to theater, or the other way round, is feasible (distinguished as two-stage hybrid procedure).Upon this rationale, cut-downs and hypoplastic left heart syndrome hybrid approaches (groups 1 and 2) were mainly performed in the cath-lab, whereas most ventricular septal defect closure, pulmonary branches balloon dilatation, and Melody insertion took place in theater .Technique:Vascular access in the cath-lab. Particularly for neonates and infants below 5 kg requiring aortic valvuloplasty. An incision is performed in the neck by the surgeon. The carotid artery is dissected and looped before purse-string or cut-down cannulation  plus open cell stent deployment through the entire length of the ductus was performed  took place in the cath-lab. Carotid artery was approached in 25 neonates for aortic valvuloplasty (22 children), ductal stent , coarctation angioplasty (one patient), and coarctation stent (one case). The jugular vein was used twice: in a 4-month-old Fallot patient on transthoracic ECMO for stenting the right ventricular outflow tract and in a 2-year-old infant with a previous Melody in the tricuspid position (which happened to be regurgitant) in whom a valve-in-valve procedure was attempted. On completing the procedure, the vessel was repaired (either stitching the cut-down or closing the purse-string suture) and the patency checked.B. Hypoplastic left heart syndrome, or alike . Six neonates with hypoplastic left heart syndrome were deemed unsuitable for conventional Norwood I technique because of low weight (1.8 kg), myocardial dysfunction, severe tricuspid regurgitation, or ECMO resuscitation. In the same period of time, nine classical Norwood were carried out (with two deaths).Four patients were “bridged” to promote bi-ventricular repair, either as an intention-to-treat (two cases) or after a decision-making in theater .Seven patients underwent subsequent atrial septostomy plus stent deployment. Another child had to be re-banded.At follow-up, four patients had a bi-ventricular repair , seven were transplanted , 16, andEventually, four out of the 10 patients died, one in each group: arch repair (ventricular arrhythmia), one transplant (pneumonia), one comprehensive repair (pulmonary hypertension), and the abovementioned in the transplant waiting list.C. Muscular ventricular septal defect  and then driven to theater (for closure under cardiopulmonary bypass) with good result .Eight children had their muscular ventricular septal defect closed by a per-ventricular approach.In four cases, provided that it was a single defect, a mini-sternotomy without cardiopulmonary by-pass was scheduled.The four remaining ones were approached through a full-sternotomy and cardiopulmonary by-pass, since other defects had to be addressed: patching of a common atrium, perimembranous ventricular septal defect, debanding, and aortic arch repair, respectively. One of the patients  was complicated by a puncture in the left ventricle lateral wall . Because154 VSD were operated on in the same lapse of time.D. Surgical dilatation of pulmonary branches (12 children). Concomitant surgical repair and pulmonary arteries dilatation was accomplished in 12 children.Three former Fallot patients had their left pulmonary branch balloon-dilated and then a biological pulmonary valve implanted on a beating-heart basis.Three children who underwent right ventricle to pulmonary artery conduit replacement  had their left pulmonary branch balloon-dilated (2) or stented (1) in the same fashion.One patient had a plug delivered in the pulmonary trunk by a perventricular puncture along with Fontan completion.Five patients with a previous “hybrid bilateral banding” had their pulmonary arteries revisited: a 3.4 kg transplant who suffered a tear in the right pulmonary artery and had a covered stent deployed, two more transplant children, and two patients (arch repair and Yasui) who were electively scheduled for branches dilatation at the time of band removal plus bi-ventricular repair.E. Melody deployment in theater (6 cases).Mitral regurgitation after a switch procedure in a neonate was unsuccessfully addressed by artificial chordal insertion and eventually treated with a Melody under cardiopulmonary by-pass and cardioplegic arrest. Unfortunately, the child died on septicemia several days later, with a well functioning valve. A second patient was successfully operated on under the same strategy.A neonate with pulmonary atresia and intact ventricular septum plus severe tricuspid regurgitation had a Melody implanted in tricuspid position, after a failed attempt of valve repair (plus conduit insertion between right ventricle and pulmonary artery).Two former Fallot patients presenting with residual VSD and pulmonary regurgitation had the ventricular septal defect addressed, plus a transannular Melody valve implanted  and balloon dilated in the pulmonary position .An infant with a right ventricle to pulmonary conduit in place was scheduled for a perventricular conduit deployment by sub-xyphoideal approach. One purse-string was stitched in the diaphragmatic right ventricle wall. The stiff wire happened to dissect the previous conduit and emergent re-sternotomy plus cardiopulmonary bypass was instituted, ending up in a surgical conduit replacement.121 percutaneous and 73 surgical pulmonary valves were implanted between 2013 and 2020 by our group.BUS absorb stent was deployed in the opposite left superior pulmonary vein under fluoroscopy.F. Pulmonary vein stenosis. A 5-month-old infant with congenital left pulmonary vein stenosis was attempted to treat percutaneously twice. Transeptal approach proved unsuccessful. In the cath-lab, by midline sternotomy, a purse-string suture was fashioned in the right superior pulmonary vein (as for a regular “vent” sucker in theater) and a sheath advanced through it. Then, a In the last 50 years, there has been an incredible evolution and expansion of surgical and percutaneous procedures for patients with congenital heart disease. Hybrid approaches offer the advantages of both disciplines together , where nSince its inception for the palliation of hypoplastic left heart syndrome , the conThe hybrid procedure is used in neonates with hypoplastic left heart syndrome as an alternative to the conventional Norwood when the risk is considered too high due to prematurity/low weight or other comorbidities, as in our 15 patients. Any comparison between Norwood and hybrid palliation is skewed, since the latter group gathers patients not amenable to Norwood and, hence, at a higher risk . Like inRegarding surgical management of ductal stent at second stage , several groups have reported their experience in handling the stented ductus/arch , 19–22, According to pulmonary arteries dilatation/stenting along with major surgical repair, our team has gained experience and confidence. Those patients can spare a visit to the cath-lab for branch ballooning/stenting either before or after surgery . InteresOur experience with Melody device is scarce; just two neonates in the mitral position, and another one in the tricuspid valve, following Boston's report . The forThe hybrid procedure is not complication-free. Learning curve and range of techniques should be born in mind. Two major drawbacks have been recorded. An accidental puncture  in a perStudy limitations. The present paper gathers a vast array of congenital conditions and hybrid procedures. Despite arbitrarily clustering the patients in categories alike, the authors are well aware of the difficulties in drawing any early conclusions provided the scarcity of data in every column . AuthorsSurgeons and cardiologists alone are often not able to achieve the best therapeutic effect in the field of optography, but the close collaboration between the two may achieve better results in some fields. This study explores both surgeon and cardiologist partnership can succeed where their isolated endeavors are not enough, which provides new ideas and ideas for the treatment of pediatric diseases.The expectations of the hybrid methods, devised for hypoplastic left heart syndrome, have been overcome by the increasing number of indications which have been successfully applied. Bridging children to biventricular repair or transplant with the hybrid bilateral banding plus ductal stenting is becoming particularly appealing. Patients' challenges and team imagination set the boundaries for this strategy. Equipment, training, and ideas are the basis for innovation, fostering the future of cardiovascular medicine.On gaining experience, the number of cases and categories will increase providing insight and more robust conclusions.As a word of caution, hybrid approaches are not complication-free, inasmuch when some procedures are custom-made and tailored to any given patient needs.giljaurena@gmail.com.Requests to access the datasets should be directed to the corresponding author at: The studies involving human participants were reviewed and approved by Hospital Gregorio Marañón's ethics committee. The patients/participants parents provided written informed consent to participate in this study.The authors specify that there is no financial, property, or intellectual aid from any commercial source. The authors state that they had full control of the design of the study, methods used, outcome parameters, analysis of data, and production of the written report.All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Background: Myocardial blush grading is considered to be a novel tool for assessment of coronary microvasculature and myocardial perfusion in patients undergoing coronary angiography and angioplasty, and its reduction identifies patients at high risk. Our study aimed to evaluate the association between acute insulin resistance and myocardial blush in non-diabetic patients with ST-segment elevation myocardial infarction (STEMI).Methods: Two hundred forty non-diabetic patients with STEMI who underwent primary percutaneous coronary intervention were consecutively recruited. The relationship of homeostasis model assessment—estimated insulin resistance (HOMA-IR) to myocardial blush and in-hospital outcome was investigated.Results: Higher HOMA-IR tertile was observed in obese patients, with hyperinsulinemia, had Killip class >1, with higher CPK-MB level and was correlated to impaired myocardial blush after adjusting for the other confounding risk factors. It was also concluded that higher HOMA-IR was independently associated with no/minimal myocardial blush after STEMI. Moreover, it was founded to be an independent predictor of pulmonary edema and impaired left ventricular systolic function.Conclusion: This study revealed that acute insulin resistance was prevalent in non-diabetic patients with STEMI and was an independent predictor for post-infarction myocardial and microvascular injury and poor in-hospital outcome.Trial Registration: The trial was registered at the registry of Clinicaltrials.gov, ClinicalTrials.gov Identifier: NCT04651842, Date of registration: 2nd December 2020 Registry URL, https://clinicaltrials.gov/ct2/show/NCT04385589?cond=Dapagliflozin+in+diabetic+patients&cntry=EG&draw=2&rank=1. Complete myocardial reperfusion and restoration of coronary microcirculatory function (CMF) is a therapeutic goal in ST-segment elevation myocardial infarction (STEMI) . HoweverIt was found that insulin resistance (IR) plays substantial role in the development of cardiac-vascular infirmities and carries bad prognostic outcome for acute myocardial infarction (AMI) .IR was found to be related to cardiac injuries on both muscular and microvascular levels after STEMI. Likewise, after adjusting for other integrals of metabolic syndrome, IR was associated with myocardial injury after elective PCI .Now, IR was assessed by the homeostatic model assessment (HOMA) index in the early phase of acute coronary syndrome in non-diabetic patients. This “acute IR,” considered a part of the acute glycol-metabolic response to stress, may be transient and also can occur even in patients without chronic glycol-metabolic derangements .Acute IR includes acute hyperglycemia and/or acute hyperinsulinemia. Hyperglycemia has the importance of prognostic relevance of hyperinsulinemia in STEMI patients, but its relationship with coronary flow is still unclear , 8. HoweMyocardial blush is a qualitative visual assessment of the amount of contrast medium filling a territory supplied by a pericardial coronary artery  was fir. DecreasThe current study hypothesis was that acute IR can occur in the early post pPCI period even in non-diabetic patients as a dynamic phenomenon, and it could be related to the development of microvascular injury. Myocardial blush is defined as a marker of coronary microvascular function; accordingly, IR was evaluated in relation to myocardial blush in nondiabetic STEMI patients treated by pPCI as a primary endpoint. The residual ST-segment elevation, post-TFC% and major adverse cardiovascular events (MACE) were secondary endpoints. The HOMA index is a simple and inexpensive marker of IR, primary used in chronic states. It was recently validated in STEMI patients as feasible for assessing IR during myocardial infarction and therefore used in the current study .*Power 3 software. With a power of 95% and type I error of 5% (α = 0.05 and β = 95%), the minimum required sample was 210 patients  for an effect size of 10% in rate of myocardial blush grade.This cross-sectional comparative study included 240 non-diabetic patients with acute STEMI selected from the Cardiology Department, Assiut University Hospital, who underwent primary percutaneous coronary intervention (PCI) between May 1, 2018 and May 1, 2019. Sample size was calculated using the GExclusion criteria were diabetic patients, renal insufficiency, advanced hepatic dysfunction, had malignancy, chronic heart failure/cardiomyopathy, prior myocardial infarction, and diseases requiring steroid therapy; patients on antioxidant supplement/therapy within 4 weeks before enrolment in the study, pregnant females, alcoholic, patients allergic to radiographic contrast, and uncooperative/refusal.Ethical approval was obtained from the Medical Faculty, Assiut University (IRB No. 17300510) and was adherent to the guidelines of the declaration of Helsinki.Proper history taking including history for the presence of cardiovascular risk factors: hypertension, diabetes mellitus, dyslipidemia; smoking and family history of premature coronary artery disease, history of ischemia, previous CCU admission, and previous PCI.2 (kilograms per square meter).Complete physical examination including body mass index (BMI) was calculated using the formula of weight/heightBlood pressure was measured in a seated position after a 10-min rest, using an electronic blood pressure monitor .Diagnosis of diabetes was made according to the criteria of the American Diabetes Association, and prediabetes was defined by fasting blood glucose of 100 mg to <126 mg/dl, 2-h plasma glucose of 140 to <200 mg/dl, or HbA1C of 5.7 to <6.5% , and hyperlipidemia was diagnosed according to the guidelines of the National Cholesterol Education Program (ATP III) , 14.Blood samples were collected in an air-conditioned and quiet room. Serum glucose, blood urea, creatinine, total cholesterol, low-density lipoprotein—cholesterol (LDL-C), high-density lipoprotein—cholesterol (HDLC), and triglycerides were assessed using a HITACHI 912 Analyzer . Insulin and creatine kinase MB isoform level were assessed by AIA 900, fluorescence enzyme immunoassay (FEIA) method (Japanese).After obtaining informed consent, the included patients were subjected to:15. Normal reference levels for HOMA-IR range between 0.7 and 2.0. HOMA-IR is a preferred estimate for insulin resistance as glucose clamp methods, the current gold standard, are resource intensive and time consuming. Several studies use 2.0 as cutoff for increased insulin resistance /405After the angioplasty procedure immediately, epicardial and myocardial reperfusion was assessed and graded on the angiograms. In each patient, the best projection was chosen to assess the myocardial region of the infarct-related coronary artery, preferably without super positioning of non-infarcted myocardium. Angiographic runs must be long enough to allow some filling of the venous coronary system, and backflow of the contrast agent into the aorta have to be present to be sure of adequate contrast filling of the epicardial coronary artery.All angiograms will be made after 400 μg of nitroglycerin intracoronary has been given immediately after the primary angioplasty procedures, and this procedure allows quantitative coronary artery analysis : First, Myocardial reperfusion had been also determined by measuring ST-segment resolution (STR) analysis so ECGs had been done on admission (first ECG) and 90 min after the primary PCI in the coronary care unit (second ECG). The second ECGs had been classified with regard to the ST segment resolution into the following grades: Normalized, defined as no residual ST segment elevation; Improved, defined as a residual ST segment elevation <70% of that on the first ECG; Unchanged, defined as a residual ST segment elevation > 70% of that on the first ECG .For all patients, postprocedural transthoracic echocardiography left ventricular ejection fraction was measured by biplane Simpson method using the end diastolic and end systolic apical four- and two-chamber views for estimation of left ventricular volume and calculation of ejection fraction. In hospital primary angioplasty procedures, major adverse cardiovascular events (MACEs) were determined and defined as the composite of death, stent thrombosis, re-infarction, cardiogenic shock, and stroke .2 and Monte Carlo exact test was used to compare the difference in the distribution of frequencies among different groups. One-way ANOVA was used to determine the mean difference between groups. Binary logistic forward regression analysis was used to define the independent predictors of MBG variables that showed significant differences among the studied groups. A value of p < 0.05 was considered statistically significant.Data entry, verification, and validation were carried out by the researcher, and analyses were performed via IBM-SPSS software . Numerical data were expressed as mean ± SD, and frequency tables with percentages were used for categorical variables. χThis study aimed to evaluate the impact of insulin resistance in non-diabetic (IR) on myocardial blush and in hospital MACE in the setting of STEMI patients treated with PCI. Non-diabetic patients (274), with anterior and non-anterior STEMI, who were admitted to the ICU during the study period, were recruited. Thirty-four patients were excluded for recently discovered diabetes mellitus, left main thrombosis, aortic valve prostheses with embolization, stent thrombosis, and defect of data counting. Hence, 240 patients  were available for analysis .The majority of the studied patients were males aged >50 years with insignificant difference between groups in relation to HOMA-IR. Moreover, acute insulin resistance as estimated by HOMA-IR tertile was significantly higher in obese, those with heart failure (Killip class >1), and higher plasma insulin level, CPK-MB, and fasting blood glucose level .Although, patients with anterior wall infarction (AWI) had insignificantly higher HOMA-IR levels, those with higher HOMA-IR experienced significantly low-grade baseline TIMI as higher tertile was founded on grade 0 baseline TIMI . Also, pIt was found that patients with MBG 0, 1, 2 had higher HOMA-IR level than those with grade 3, and those who had unchanged ST segment in their ECG after reperfusion had higher HOMA-IR level. Furthermore, postprocedural TIMI frame count (TFC) was longer in those with higher HOMA-IR level. Patients with low, intermediate HOMA-IR levels showed higher postprocedural TIMI flow grade than Grade 3 .A higher level of HOMA-IR was detected in those with post MI pulmonary edema; however, prolonged hospital stays, arrhythmias, LVF, cardiogenic shock, re-infarction, and early stent thrombosis complicated higher HOMA-IR level but with insignificant difference .p = 0.001) and by 10% in the multivariate analysis  . Importantly, HOMA-IR level is considered an independent risk for decreasing myocardial blush, i.e., with one unit increase in HOMA-IR level, there was decreasing myocardial blush by 20% in univariate analysis  .The present study analyzed IR in the acute phase of STEMI in non-diabetic patients treated by pPCI. First, it confirmed that acute IR in the early post pPCI period is common even in non-diabetic patients; second, IR, as estimated by HOMA-IR, affects myocardial perfusion especially MBG; and third, IR was related to the in-hospital MACE.IR in the early phase of STEMI is considered part of the acute glycol-metabolic response to stress  GenerallMore cardiac necrosis was reported in those with higher IR. The relationship between acute IR in non-diabetic STEMI patients and myocardial damage in terms of peak enzymes was previously reported , 29. In per se predicted impaired epicardial flow before pPCI  were considered important predictors of markedly reduced myocardial blush. This may be explained by IR in the setting of STIMI being associated with poor myocardial reperfusion, impaired coronary microcirculation  and collThe current study revealed that acute IR was prevalent in non-diabetic patients with STEMI and was identified as an independent predictor of post infarction myocardial and microvascular injury. Likewise, it was found to be associated with poor in-hospital outcome.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by prof/Mahmoud abdel-Aleem- Medical ethics committee IRB no.17300510. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.SK and MA conceptualized and designed the study, conducted a literature search, conducted the clinical studies, prepared the experimental study manuscript, and edited and reviewed the article. AH was in charge of the definition of intellectual content, literature search and manuscript review, clinical studies, experimental studies, and data acquisition. GS conducted the clinical studies, experimental studies, and acquired the data. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


There are few non-invasive monitoring methods that can reliably predict fluid responsiveness (FR) in children. Here, we interrogate the value of doppler ultrasound evaluation of passive leg raising (PLR)-induced changes in stroke volume (SV) and cardiac output (CO) as a predictor of FR in children with mechanical ventilation after congenital cardiac surgery.A total of 40 children with mechanical ventilation following congenital cardiac surgery, who required volume expansion (VE) were included in this study. Hemodynamic parameters such as heart rate (HR), mean arterial pressure (MAP), SV, and central venous pressure (CVP) were monitored before and after PLR and VE. Besides, we assessed changes in SV and CO by bedside ultrasound. Patients showing > 10 % increase in SV in response to VE were considered to be responders (26 patients), while the rest (14 patients) were defined as non-responders.p < 0.001 and r = 0.374, p = 0.017, respectively), and the area under the ROC curve (AUC) of ΔSV-PLR was 0.879 . The best cut-off value for ΔSV-PLR in predicting FR was 13 %, with its sensitivity and specificity were 81.8 and 86.3 %, respectively. ΔCVP, ΔHR, and ΔMAP were weak predictors of FR in the children.Our data demonstrated that ΔSV-PLR and ΔCO- PLR were positively correlated with ΔSV-VE (r = 0.683, Our study demonstrated that SV changes, as evaluated by noninvasive ultrasound combined with PLR, could effectively evaluate FR in children under mechanical ventilation after congenital cardiac surgery. Proper fluid loading is pivotal in maintaining hemodynamic stability in children who undergo congenital cardiac surgery . ClassicPassive leg raising (PLR) is a simple repeatable self-replenishing fluid method done to shift venous blood from the lower limbs toward the intrathoracic compartment , 9. TranHere, we tested whether PLR related changes in SV and CO as monitored by bedside echocardiography could accurately predict FR in children with mechanical ventilation after cardiac surgery.The study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of Shangrao Fifth People's Hospital (No.2016-12-01). All participants gave written informed consent prior to their enrollment in this study.− 1·h− 1 urine output for at least 1 h), mottled skin, oliguria (less than 0.5 ml·kg− 1·h− 1 diuresis), 1.5-fold increase in arterial blood lactic acid, acute kidney failure, or clinical and laboratory signs of extracellular dehydration [This prospective observational study was carried out at the integrated Intensive Care Unit of the Fifth People’s Hospital of Shangrao City  from December 2016 to July 2017. We enrolled a total of 48 patients who were under mechanical ventilation following cardiac surgery, and whose attending physician conducted a fluid challenge. The execution of the fluid challenge dependent on at least one clinical sign of inadequate tissue perfusion, with no contraindications for infusion. The clinical signs of inadequate tissue perfusion were characterized by acute circulatory failure 2. SV and CO were measured with the equations: SV = VTI × aortic area, and CO = SV × HR. The aortic area was considered to be stable during the trial and was measured only once in the initial measurement. Every VTI measurement was taken based on two or three measurements in one breathing cycle. All of the measurements were conducted by a cardiologist.A 4-5.5fr central venous catheter was inserted into the right internal jugular vein or the right/left subclavian vein to monitor CVP, while a 7 cm 3fr arterial catheter was inserted into the right or left femoral artery to monitor dynamic blood pressure, before operation. MAP was calculated as MAP = /3. The standard transthoracic probe (3SP-D) of GE VIVIVIXE9 Doppler echocardiography was used to measure SV. On the five chambers apical view, the aortic blood flow was recorded using pulsed Doppler, with the sample volume placed on the annulus aorta. A velocity-time integral (VTI) of the aortic blood flow was also measured. The aortic valve area was calculated from the diameter of the aortic orifice, measured at insertion of the aortic cusps, as aortic area = The patients were placed in a supine position, with the upper body parts being 45° higher (Base 1) and four hemodynamic parameters  were measured. Afterwards, the upper parts of the body were lowered to achieve a horizontal position and the lower extremities raised to 45° (Base 2), and then the four hemodynamic parameters were measured again within 30 s to 1 min. The patients were placed back to the initial position  for 10 min and the hemodynamic parameters were remeasured. Besides, the four hemodynamic parameters were again measured immediately following the administration of the bolus of the intravenous fluid challenge using 10 ml/kg of 5 % albumin in 15 min. The patients showing > 10 % increase in SV in response to the VE were considered responders, while the rest were defined as non-responders. All the procedures were conducted while the patients were kept fully sedated, and the parameters such as the use of vasoactive drugs, sedatives and mechanical ventilation remained unchanged.p < 0.05 was considered to be statistically significant. All the statistical analyses were performed with IBM SPSS 23.0 .Continuous variables were presented as the mean ± standard deviation if normally distributed, or as a median (range) if the distribution was not normal. Student’s unpaired t-test or the Mann–Whitney U-test was used to evaluate group differences. To assess the correlation between ΔSV-VE and PLR related ΔSV, ΔMAP, ΔHR, ΔCVP, or ΔCO, linear regression analysis was performed. Linear correlations were tested using the Pearson test and linear regression method. To determine the ability of all the variables to predict fluid responsiveness, receiver operating characteristic (ROC) curves were generated, and the area under the ROC curve was calculated. The ROC curves were compared using the Hanley–McNeil test . Youden’n = 18, 45 %), tetralogy of fallot (TOF) , atrial septal defect (ASD) , or ASD + VSD . There was no significant difference in age, gender, vasoactive drug usage score, ventilator parameters, and indication for ICU stay (p > 0.05). The clinical characteristics for the two groups are shown in Table A total of 48 patients who were under mechanical ventilation with presumed hypovolemia and were considered for VE were included in the study from December 2016 to December 2017. Among these eligible patients, 8 were excluded because of poor transthoracic insonation. Therefore, 40 patients  with mean age of 5.41 ± 3.25 years were included in the study. There were patients with ventricular septum defect (VSD) (p > 0.05) between Base 3 and Base 1. The hemodynamic parameters before and after PLR and VE are listed in Table ΔSV in 26 children (responders) increased by more than 10 % from the base 3 value after VE, while ΔSV in 14 patients (non-responders) increased by less than 10 %. There were no significant shifts in all hemodynamic changes . The highest area under the ROC curve (AUC) for ΔSV-PLR (0.879 ± 0.069) successfully predicted FR in the patients . The correlation between Δ-PLR and ΔSV-VE is shown in Table The ΔSV-PLR and ΔCO- PLR were positively correlated with ΔSV-VE (Pearson’s The optimal ΔSV-PLR threshold for predicting FR was 13 %, and its sensitivity and specificity were 81.8 and 86.3 %, respectively. The positive and negative predictive cut-offs were 85.0 and 82.0 %, respectively. The optimal threshold values and associated sensitivities and specificities are presented in Table Prediction of FR is critical in fluid therapy after cardiac surgery, especially in children. Significant changes in ventricular systolic and diastolic functions after cardiac surgery often lead to difficulties in predicting FR , 16. HerPLR is a simple, noninvasive and repeatable method to change the cardiac preload , 9, 17. In recent years, bedside ultrasonography has been considered as a noninvasive, real-time, convenient, low-cost, and repeatable tool for monitoring hemodynamics , 19–21. Whereas CVP, MAP, and HR were relatively easy to monitor, we did not observe any correlation with ΔSV-VE. Our data showed that ΔCO-PLR could predict FR, with an optimal threshold of 8 %, sensitivity of 81 % and specificity of 71 %. But the correlation between ΔCO-PLR and ΔSV-VE was not comparable to that of the ΔSV-PLR, which may be due to the influence of the HR on CO measurement. Consistent with the previous findings, our study found that ΔSV-PLR can better predict FR compared with the other PLR-Δs .There are some limitations in this study. First, echocardiographic measurement errors may have occurred, even though the same expert obtained all echocardiographic data. Second, because of the different types of congenital heart diseases and the diverse changes in cardiac structure after operation, our results cannot be extrapolated to other types of congenital heart diseases and to children of all ages, because leg elevation in newborns or infants obviously does not have the same volume effect as leg elevation in older children. Third, based on previous studies, we defined a 10 % increase in SV with rapid fluid loading as FR-positive. Whether the 10 % cut off is the appropriate threshold needs further research. Another limitation is that it is also a small sample, non-blinded study, and the results may not be applicable to other centers. Finally, someone is a fluid “responder” does not mean that they need a fluid bolus. If a healthy normally hydrated person is given a fluid bolus, their stroke volume will also increase, however, that does not mean that they need fluid. This is probably why the increases in MAP overall are very modest in our study even in responders. Therefore, further investigations of high-quality are needed to confirm our findings.In conclusion, our study demonstrated that assessment of the SV changes by noninvasive ultrasound combined with PLR could be used to evaluate fluid responsiveness in children under mechanical ventilation after congenital cardiac surgery.


The loading conditions must be accounted for when evaluating RV systolic function by 2D-STE parameters.(1) Background: Right ventricular (RV) strain parameters derived from the analysis of the tricuspid annular displacement (TAD) are emergent two-dimensional speckle tracking echocardiography (2D-STE) parameter used for the quantitative assessment of RV systolic function. Few data are available regarding 2D-STE parameters and their dependency on RV preload. Our aim was to evaluate the effect of an acute change in RV preload on 2D-STE parameters in healthy volunteers. (2) Methods: Acute modification of RV preload was performed by a fluid challenge (FC): an infusion of 500 mL of 0.9% sodium chloride was given over 5 min in supine position. Preload dependency (responder group) was confirmed by a stroke volume increase of at least 10% measured by echocardiography. (3) Results: Among 32 healthy volunteers, 19 (59%) subjects were classified as non-responders and 13 (41%) as responders. In the responder group, the tricuspid annular plane systolic excursion (TAPSE) significantly increased (20 (20–23.5) mm to 24 (20.5–26.5) mm;  Two-dimensional 2D) transthoracic echocardiographic (TTE) assessment of the right ventricular (RV) systolic function is challenging, requiring a multi-parametric approach due to the complex geometry of the RV and its retrosternal location but also to the loading dependency of most echocardiographic parameters ,2. ConveD transthTwo-dimensional speckle-tracking echocardiography 2D-STE) is a relatively new, non-invasive echocardiography technique that allows an objective and quantitative assessment of RV systolic function D-STE is  and tricTAD parameters are angle-independent, but their main advantage compared to RV longitudinal strain is their independence regarding endocardial borders definition ,4,8.However, current guidelines do not provide references values for 2D-STE parameters but rather lower limits of normality for vendor-dependent software . RecentlBesides, recent studies have shown that under specific conditions, 2D-STE parameters are dependent on the patient’s blood volume ,10 and tAccording to the Frank Starling relationship, we hypothesized that an FC-induced acute increase of RV volume should be followed by an increase in RV systolic function and therefore by an increase in RV 2D-STE parameters value.The aim of this study was to evaluate the effect of an acute change in preload on 2D-STE parameters in healthy volunteers. This acute change in preload was performed by an infusion of 500 mL of saline over 5 min. Preload dependency of 2D-STE parameters was defined by a 10% increase of stroke volume (SV) measured by transthoracic echocardiography after FC.This study was an ancillary study of the PORTEAU study (NCT03589261) evaluating portal blood flow after FC at Amiens University Hospital between September 2018 to November 2019. We retrospectively analysed echocardiographic data from 37 healthy volunteers who participated in this study. We excluded 5 patients in whom it was difficult to assess RV speckle tracking analysis because of poor imaging quality. The final study population consisted of 32 healthy volunteers .The acute modification of the subjects’ RV preload was performed by a FC . AccordiThe volunteers’ blood volume was standardized as best as possible. All volunteers had been fasting from 00:00 a.m. and were included in the study between 8:00 and 11:00 a.m. After baseline TTE, a FC was realised by the infusion of 500 mL of 0.9% sodium chloride  over 5 min via a 16-gauge peripheral vein line in the left arm. The post-FC TTE was performed 15 min after the FC. Subjects were monitored for 2 h after the post-FC TTE to detect any FC-related adverse events. We collected the following demographic data for all subjects: weight, height, and body mass index (BMI). The following baseline and post-FC experimental data were also collected: systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP) with an automated pneumatic device and heart rate (HR) using a continuous 3-line electrocardiogram.VTI) was averaged on three pulse consecutive Doppler measurements in a 5-chamber view [area) in a long axis parasternal view. Doppler stroke volume (SV) was estimated by the product of LVOTarea and LVOTVTI [A standardized TTE protocol was performed according to recent guidelines  and usinber view . The cha LVOTVTI . RV syst2D-STE parameters were analysed offline using the commercial software package available on cart with Philips CX50 echocardiography machine . 2D-STE parameters were analysed in one loop, and results were the average of 3 measured. All 2D-STE parameters were performed offline by two observers (CB and MC) blinded to fluid responsiveness status.For RV strain analysis, the left-ventricle-specific strain software was used because RV-specific software was unavailable. The region of interest (ROI) was generated automatically and adjusted manually whenever the automated one was of poor quality. A full-wall approach was used for RV strain analysis: endocardial border of the RV strain was manually traced at end systole and automatically adjusted to include the entire myocardium. The frame rate ranged between 60 and 80 frames/second. Apical four-chamber views focused on the RV were acquired for the 2D RV free wall longitudinal strain (RVFWLS) analysis according to current guidelines  Figure A. RVFWLSTAD parameters measurement were also performed on the apical four-chamber view.lat) and at the interventricular septum (TADsep). RV longitudinal shortening (RV-LS) was calculated as maximum end-systolic displacement (LES) of the mid-annular point from the measured annular motion and expressed in percent of the end diastolic RV longitudinal dimension (LED): 100 × (LED − LES)/LED  at the insertion of the anterior tricuspid valve leaflet  and (2) of the septal leaflet into the tricuspid annulus and (3) at the RV apex C. The soLES)/LED C. The miData are expressed as mean ± standard deviation (SD), median (interquartile range) or numbers (percentage), as appropriate. Variables were compared using Wilcoxon–Mann–Whitney, chi-square, or Wilcoxon rank-sum tests, as appropriate. To evaluate the intra-observer and inter-observer variability for offline analysis, data of 10 healthy volunteers were randomly selected and analysed by two operators (CB and MC) with at least a 1-week interval between the two analyses. Each operator was blinded to the results of the other. The inter-observer and intra-observer’s reliability of 2D-STE measurements were assessed using intraclass correlation coefficient (ICC) as recommended .p < 0.05.All statistical analyses were performed with IBM SPSS software . The limit of statistical significance was n = 28). Hemodynamic parameters before and after FC are displayed in p = 0.02) and in HR (64 bpm (58–71) to 60 bpm (54–69); p = 0.03) after FC. Left ventricular (LV) and RV echocardiographic parameters before and after FC are reported in p = 0.01), while IVC collapsibility index decreased (p = 0.001). The only RV systolic parameter significantly affected by FC was RV4CSL (−22.6% (20.7–25.4) to −23.5 (22.0–26.1); p = 0.05).Thirty-two healthy volunteers were included from September 2018 to November 2019. The median age was 26 (24–28) years, and 87% were male (p ≥ 0.09) (p < 0.018), while RV-S’ and FAC were not significantly improved . RV strain parameters (RVFWLS and RV4CLS) were associated with preload dependency (−23.5% (22.3–27.3) to −25% (24–29.6); p < 0.03) and −22.8% (20.4–30.7) to −23.7% (21.2–27); p < 0.02, respectively) (p ≥ 0.27). In the responder group, IVC collapsibility index decreased after FC (from 35.5 (28–55)% to 24 (22–30), p = 0.001).After FC, 19 (59%) subjects were classified as non-responders and 13 (41%) as responders with an increase in SV of more than 10%. In the responder group, there was no significant difference for hemodynamic parameters before and after FC  . Regardictively) , while Tp ≥ 0.11).After FC, 19 (59%) patients did not increase their stroke volume more than 10% relative to baseline and were therefore in the non-responders group . In thisn = 32/37)). Overall, the feasibility of the speckle tracking parameters was good  among 2D-STE parameters, RVFWLS, and RV4CSL are preload-dependent, while TAD seems preload-independent; (2) among 2D RV conventional parameters, only TAPSE is preload-dependent; and (3) the reproducibility of 2D-STE measurements is excellent.Due to its large availability and safety, 2D echocardiography is the first-line non-invasive imaging modality used to assess the RV systolic function by a standardized multiparametric approach ,9. HowevThe introduction of new echocardiographic parameters, such as 2D-STE parameters, has significantly improved our ability to assess RV systolic function. These parameters are highly correlated with CMR measurements even if CMR evaluate RV in three dimensions . HoweverCardiovascular adaptation to increased preload is a pathophysiological mechanism supported by many factors. According to Frank–Starling law, there is a positive relationship between preload and stroke volume. However, this relationship is not linear but rather traces a curve. Accordingly, once a concrete preload value has been reached, further increments do not give rise to significant additional stroke volume elevation. Preload dependency is the capacity of the heart to modify stroke volume in response to changes in preload and depends on the basal preload value and the zone of the Frank–Starling curve in which both ventricles are operating. Each individual patient can present a series of ventricle function curves and therefore a different response for the same preload increase. In hemodynamically unstable patients, the management of fluid therapy is crucial because only 50% of patients are preload responders . In our To our knowledge, there are few data on RV preload dependency of 2D-STE parameters in healthy volunteers. Garcia-Lopez et al.  reportedOur study showed a significant increase in RV4CLS (+2.4%) and in RVFWLS (+1.6%) after FC when SV increased significantly (+13 mL) , suggestRV contraction is mainly related to the longitudinal contraction of fibres (up to 80%) that shorten the long axis and attract the tricuspid annulus toward the apex . In ordelat was 22.7 (20.5–25) mm and 15.2 (13.7–17.3) mm for TADsep. Those values are consistent with prior studies in healthy volunteers [lat and 14 ± 1.9 for TADsep [TAD is a fast, automated, and reproducible parameter that provides information on local displacement of the tricuspid annulus toward the apex. In our study, median TADlunteers ,8,19. Inwas 22.7 .5–25 mm lat measurement evaluates its shortening toward the RV apex. Data on TAD parameters in situation of preload dependency are scarce. However, in clinical situation of increased afterload, TADlat parameters seemed to be superior to TAPSE for identifying RV dysfunction with a different cut-off value for each parameters [To our knowledge, our study is the first to show that TAD parameters were preload-independent in healthy volunteers. Even if the measurements of TAPSE and TAD parameters are both based on the displacement of the tricuspid annulus, they are not interchangeable . TAPSE mrameters . BecauseDue to their reproducibility, angle independence, and ease of measurement, TAD parameters can be used in many clinical situations and myocardial disease. TAD parameters can be use in operating room for monitoring RV dysfunction with transoesophageal echocardiography  or in daOur study has several limitations: first, it is possible that infusion of larger volume would have led to significant changes in 2D-STE parameters or in 2D conventional parameters. However, our results were comparable to those of the study using passive leg raising, which is a dynamic manoeuvre allowing to mobilize 300 mL of blood in order to induce a change in preload ,15. MoreSecondly, five volunteers were excluded for poor image quality. Indeed, the image quality and the RV focus view can impact the ability to measured 2D-STE parameters and thus affect the reproducibility of 2D-STE parameters. All echocardiograms were analyzed by a single vendor’s software, and the QLAB software had no specific ROI for RV strain analysis. One another important limitation is that, unlike RVFWLS or RV4CSL, which are widely available, TAD parameters are only provided by Philips Healthcare and not by other constructors. In our study, regional strain analysis was assessed in a 2D four-apical chamber view. Recent studies have shown that the three-dimensional approach can improve the assessment of global and regional RV systolic function ,25. HoweThe results of our study have not been compared with other techniques as CMR especially because CMR and echocardiography techniques are not interchangeable for RV strain evaluation . FinallyOur study demonstrates that, in young healthy volunteers, RVFWLS, RV4CLS, and TAPSE are associated with preload dependency, while 2D-STE TAD parameters are not. Our study also shows that 2D STE parameters are highly reproducible. Therefore, this study shows that loading conditions should be taken into account to evaluate RV systolic function with 2D-STE parameters.


In clinical practice, many patients with right heart failure (RHF) have elevated pulmonary artery pressures and increased afterload on the right ventricle (RV). In this study, we evaluated the feasibility of RV augmentation using a soft robotic right ventricular assist device (SRVAD), in cases of increased RV afterload.In nine Yorkshire swine of 65–80 kg, a pulmonary artery band was placed to cause RHF and maintained in place to simulate an ongoing elevated afterload on the RV. The SRVAD was actuated in synchrony with the ventricle to augment native RV output for up to one hour. Hemodynamic parameters during SRVAD actuation were compared to baseline and RHF levels.2 and 1.26 (IQR 1.05–1.57) L/min/m2 at first and second baseline. Upon PA banding RV CI fell to a median of 0.79 (IQR 0.63–1.04) L/min/m2. Device actuation improved RV CI to a median of 0.87 (IQR 0.78–1.01), 0.85 (IQR 0.64–1.59) and 1.11 (IQR 0.67–1.48) L/min/m2 at 5 min (p = 0.114), 30 min (p = 0.013) and 60 (p = 0.033) minutes respectively. Statistical GEE analysis showed that lower grade of tricuspid regurgitation at time of RHF (p = 0.046), a lower diastolic pressure at RHF (p = 0.019) and lower mean arterial pressure at RHF (p = 0.024) were significantly associated with higher SRVAD effectiveness.Median RV cardiac index (CI) was 1.43  L/min/mShort-term augmentation of RV function using SRVAD is feasible even in cases of elevated RV afterload. Moderate or severe tricuspid regurgitation were associated with reduced device effectiveness.The online version contains supplementary material available at 10.1007/s13239-021-00562-7 In the majority of cases, right heart failure (RHF) results from a progression of left heart failure, and is associated with elevated pressures in the pulmonary circulation.9In recent work, our group has suggested the concept of soft robotic ventricular assist devices.The advantage of this approach is the considerable reduction of the surface area of foreign material that comes into contact this blood, greatly reducing the risk of thromboembolic complications. There may also be reduced cytokine stimulation and reduced shear stress on blood cells. Moreover, mimicking the native free-wall and septal approximation during systole avoids paradoxical septal motion and favors optimal hemodynamics of both the right and left ventricle.We have previously demonstrated the feasibility of optimizing the actuation and placement of soft robotic assist devices, such that secondary mitral valve insufficiency is minimized during systole.13in vivo conditions mimicking RHF with elevated pulmonary artery pressures.In this study, we describe the performance of a septally braced SRVAD in Nine Yorkshire swine 65–80 kg were used for the experiments. All animals received humane care according to the 1996 NIH guidelines for the care and use of laboratory animals. Boston Children Hospital’s institutional animal care and use committee reviewed and approved the study protocol.The experiments were performed under monitored general anesthesia. The animals were fully ventilated typically in volume control mode with a positive end expiratory pressure of 4 mmHg. A lidocaine continuous infusion of 5–20 mcg/kg/minute was typically started before manipulation of the heart and maintained as prophylaxis against arrhythmia. A baseline Dopamine infusion of 2 mcg/kg/min was maintained.Surface ECG electrodes were placed, a median sternotomy performed, and fluid filled catheters for pressure monitoring inserted into the right atrium, distal pulmonary artery and distal ascending aorta. A pressure volume catheter  was inserted into the RV via the ventricular apex and controlled for correct placement and measurement. Ultrasonic Transonic PS flow probes  were placed around the ascending aorta and the pulmonary artery to record the outputs of the left and right ventricles respectively. Baseline hemodynamics were then recorded using the Labchart data recording system . Baseline echocardiography with focus upon ventricular and valve function was performed.The SRVAD was placed under echocardiographic guidance on the beating heart, as previously described.Acute RHF was created by pulmonary artery banding. A cotton umbilical tape 0.32 cm wide  was used for umbilical banding. For the purposes of the experiment, the tape was marked into 2 mm. lengths to allow precise reduction of the pulmonary artery circumference. The band was placed around the proximal main pulmonary artery at least 2 cm distal to the pulmonary valve and proximal to the flow and pressure probes. The position was maintained by fixing the band to the posterior pulmonary artery wall using a 5/0 prolene stitch. Using a tourniquet system, the main pulmonary artery lumen is gradually occluded by tightening the band in 2-mm increments. RHF is achieved once the cardiac output falls below 60% of baseline. The band is left in place and after allowing a period of stabilization, the RHF baseline data is recorded.SRVAD was then actuated in synchrony with the heart rhythm based on detection of the RV pressure signal. The supplementary video material shows a video of the RVAD actuation. SRVAD triggers just as the RV pressure begins to build at the beginning of systole and remains actuated for 35% of the cardiac cycle. SRVAD actuators relax in synchrony with the heart. Hemodynamics were recorded at 5, 30 and 60 min of actuation.All echocardiograms were reviewed and scored by a single observer experienced in cardiac imaging. Tricuspid regurgitation grade was categorized as 0 = None or Trivial, 1 = Mild, 2 = Moderate and 3 = Severe TR. In-between grades were denoted by a 0.5 added to the lower grade. Video 2 demonstrates an example of an animal with trivial tricuspid regurgitation and another with severe tricuspid regurgitation following RHF creation.p < 0.05 was used to determine statistical significance.Data from the periods; baseline, device implanted, right heart failure, 5, 30 and 60 min actuation were collected. In each period, representative data covering at least 15 s duration was extracted from the continuous hemodynamic traces, using the Labchart program. Because of the variation in animal size, cardiac output and stroke volume were adjusted to BSA to generate a cardiac index (CI) and stroke volume index (SVI). Continuous variables were summarized as median and interquartile range and categorical variables as frequencies and percentages. Comparisons of continuous data between specific time points were done using the Wilcoxon signed ranks test. Generalized estimating equation (GEE) was used to model the change in each parameter over time while taking into account repeated measurements within an animal and adjusting for BSA, while implementing a Gaussian family and identity link function for continuous outcome data. All statistical analyses were performed using Stata version 15.0 . A two-tailed significance threshold of 2 at the first baseline and 1.26 (IQR 1.05–1.57) L/min/m2 at second baseline measurement. Upon PA banding RV cardiac index fell to a median of 0.79 (IQR 0.63–1.04) L/min/m2. SRVAD actuation resulted in an improvement of RV cardiac index to a median of 0.87 (IQR 0.78–1.01), 0.85 (IQR 0.64–1.59) and 1.11 (IQR 0.67–1.48) L/min/m2 at 5 min (p = 0.114), 30 min (p = 0.013) and 60 min (p = 0.014) respectively. The median RV stroke volume index at first and second baseline measurement were 18 (IQR 14–22) mL/beat/m2 and 12 (IQR 10–15) mL/beat/m2 respectively. RV stroke volume at the point of RHF was 8 (IQR 6–10) mL/beat/m2. After device actuation, median stroke volume index was 9 (IQR 7–10) mL/beat/m2 at 5 min (p = 0.198); 7 (IQR 5–16) mL/beat/m2 at 30 min (p = 0.273); and 10 (IQR 6–14) mL/beat/m2 at 60 min (p = 0.286) of actuation. There was a positive correlation between the RV cardiac index improvement at 5 min to subsequent timepoints at 30 min  and one hour . Similarly, augmentation in RV stroke volume at 5 min was associated with the subsequent augmentation at 30 min (r = 0.486 p = 0.329) and 1 h . One-hour RV support was completed in four animals. In five animals 5–30 min support was completed. The effect of SRVAD actuation on RV cardiac index and RV stroke volume index are illustrated in Fig. 2 first baseline and was 1.23 (IQR 1.07–1.36) L/min/m2 at second baseline. Median LV CI fell to 0.88 (IQR 0.69–0.92) L/min/m2 upon creation of RHF. LV cardiac index at was 1.01 (IQR 0.85–1.08), 0.96 (IQR 0.91–1.19) and 0.98 (IQR 0.89–0.98) L/min/m2 at 5 min (p = 0.132), 30 min (p = 0.019) and 60 min (p = 0.033) of device actuation respectively. LV stroke volume index was 14 (IQR 12–20) mL/beat m2 at first baseline and was 11 (IQR 9–13) mL/beat/m2 at second baseline measurement. Stroke volume index reduced to 8 (IQR 6–9) mL/beat/m2 upon RHF creation and was 10 (IQR 7–11) mL/beat/m2, 8 (IQR 7–9) mL/beat/m2 and 9 (IQR 8–11) mL/beat/m2 at 5, 30 and 60 min of device actuation. Overall LV effective LV augmentation was achieved in animals where effective RV augmentation was also achieved  but was not significant at 30 min (p = 0.09) and 60 min (p = 0.875).Mean PA pressure was 15 (IQR 14–16) mmHg at first baseline, 21 (IQR 19–24) mmHg at second baseline measurement. Mean PA pressure, measured distal to the PA band, was 18 (IQR 14–22) mm Hg at RHF and remained relatively unchanged during the device actuation at 20 (IQR 16–21) mmHg, 21 (IQR 18–25) mmHg and 19 (IQR 18–21) mmHg at 5, 30 and 60 min respectively. Maximal PA pressure increased from a 23 (IQR 21–27) mmHg at RHF to 27 (IQR 23–32) mmHg, 30 (IQR 27–32) mmHg and 28 (IQR 27–29) mmHg, 5, 30 and 60 min of device actuation. The change in maximal PA pressure was statistically significantly different from the RHF reading within 5 min of device actuation (p = 0.012), 36 (IQR 32–43) mmHg at 30 min (p = 0.063) and 34 (IQR 30–36) mmHg at 60 min actuation (p = 0.875).RV end diastolic pressures were 4 (IQR 3–5) mmHg, 6 (IQR 6–8) mmHg, 7 (IQR 3–8) mmHg, 6 (IQR 2–8) mmHg, 5 (IQR 4–7) mmHg and 3 (IQR 2–6) mmHg at first baseline, second baseline, RHF, 5, 30 and 60 min actuation respectively. Maximal RV pressure was 22 (IQR 19–27) mmHg at baseline and 28 (IQR 27–33) mmHg firsts and second baseline measurement respectively. Upon RHF creation maximal RV pressure was 32 (27–35) mmHg. Maximal RV pressure increased to 38 (IQR 35–43) mmHg at 5 min (p = 0.098), 30 min (p = 0.094) and 60 (p = 375) min of device actuation.Median systolic pressure was 82 (IQR 74–89) and 56 (IQR 51–62) mmHg at first and second baseline measurement, and it was 43 (IQR 39–49) mmHg at RHF. Systolic pressure was 49 (IQR 42–55) mmHg, 47 (IQR 46–49) mmHg and 47 (IQR 42–53) mmHg at 5 min (p = 0.496), 34 (IQR 33–36) mmHg at 30 min (p = 0.438) and 34 (IQR 32–38) mmHg at 60 min actuation (p = 0.375).Mean arterial pressure was 62 (IQR 57–62) mmHg at first baseline and 46 (IQR 35–49) mmHg at second baseline. The mean arterial pressure fell to 34 (IQR 29–37) mmHg upon RHF creation and was 37 (IQR 34–38) mmHg at 5 min (p = 0.004), 30 min (p = 0.688) and 60 min respectively (p = 0.875).The fraction of RV/Systemic fraction was 0.26 (0.25–0.29) and 0.57(0.49–0.64) on first and second baseline measurements and was 0.73 (0.7–0.77) at RHF. The RV/Systemic fraction was 0.78 (0.76–0.82), 0.78 (0.68–0.91) and 0.65 (0.59–0.81) at 5 min , 30 min (p = 0.197), and 60 min (p = 0.149) of device actuation is associated with a lower grade of tricuspid regurgitation (TR). Similarly stroke volume improvement at 5 min (p = 0. 053), 30 min (p = 0.231), and 60 min (p = 0.123) of device actuation tended to be better at low grades of TR. A lower systemic diastolic pressure (p = 0.019) and lower mean arterial pressure (p = 0.024) were associated with improved RV cardiac index change Video 2: A video showing the SRVAD actuation in an animal with trivial tricuspid regurgitation following right heart failure creation and anther with severe tricuspid regurgitation. Supplementary material 2 (MP4 2763 kb)Below is the link to the electronic supplementary material.


Characterize incident heart failure (HF) phenotypes among patients with various chronic inflammatory diseases (CIDs).Several CIDs are associated with increased HF risk, but differences in HF phenotypes across CIDs are incompletely understood. No prior studies to our knowledge have manually adjudicated HF phenotypes across a CID spectrum.We screened for patients with—and controls without—CIDs who had possible HF, then hand-adjudicated HF endpoints. Possible HF resulted from a single HF administrative code; HF was deemed definite/probable vs. absent using standardized, validated criteria. We queried adjudicated HF patients' charts to define specific HF phenotypes, then compared clinical, demographic, and HF phenotypic characteristics for HF patients with specific CIDs vs. non-CID controls using Fisher's exact test.Out of 415 possible HF patients, 192 had definite/probable HF. Significant differences in HF phenotypes existed across CIDs. Isolated right-sided HF was present in 27.8% of patients with SSc and adjudicated HF, which is more than twice as common as it was in any other CID. Left ventricular systolic dysfunction was most common in patients with HIV and lupus (SLE); mean LVEF was 45.0% ± 18.6% for HIV and 41.3% ± 17.1% for SLE, but was 57.7% ± 10.7% for SSc. Those with HIV and multiple CIDs were most likely to have coronary artery disease.Different CIDs present with different phenotypes of physician-adjudicated HF, potentially reflecting different underlying inflammatory pathophysiologies. Larger studies are needed to confirm these findings, as are mechanistic studies focused on understanding specific immunoregulatory contributors to HF. Chronic inflammation plays a central role in the pathogenesis of myocardial dysfunction and heart failure (HF) . Yet, deUsing electronic health record-based data stored in the Northwestern Medicine Enterprise Data Warehouse (NMEDW) , a large cohort of patients with CIDs and non-CID controls receiving regular outpatient care was created. Regular outpatient care was defined as at least one in-person outpatient visit every 2 years during the period of observation (1/1/2000 to 1/1/2019) in a large urban medical system. The NMEDW stores clinical observations of >6.6 million people, and its external validity is demonstrated by the fact that previous investigations of HIV-associated cardiovascular disease using this database yielded findings comparable to those of multicenter U.S. HIV cohorts –10. The We identified adults 18 years of age and older with CIDs during the above stated period of observation by using the following validated criteria: for SSc , inflammA1c >6.5% or prescription of antidiabetic medications anytime prior to 1 year after the baseline date  anytime prior to 1 year after the baseline date , 25. Givine date . The preOur adjudication protocol was based on a method we previously adapted from the Multi-Ethnic Study of Atherosclerosis for adjudicating events in electronic health records-based cohorts . As inciPatients who screened positive for “possible heart failure” subsequently underwent manual chart review to determine whether “probable heart failure” was present at the time of incident HF diagnosis. This designation was based on fulfilling all 3 of the following criteria: (1) the patient had signs or symptoms of HF ; (2) the physician diagnosed HF ; and (3) the patient was prescribed medication for HF .2); (4) diastolic dysfunction ; (5) moderate-severe valvular disease; or (6) evidence of right ventricular failure . Definite and probable HF events were combined and considered HF events for the purpose of these analyses. In addition to determining whether HF was present or absent, we adjudicated phenotype-related factors, such as the presence or absence of CAD (as previously specified) and right vs. left-sided HF (based on echocardiographic parameters), as well as whether or not the patient received a cardiac MRI.Patients screening positive for “probable heart failure” underwent further manual chart review to determine whether “definite heart failure” was present at the time of incident HF diagnosis. This designation was made by fulfilling at least 1 of the following criteria: (1) chest x-ray showed signs of volume overload; (2) echocardiogram showed evidence of HF; or (3) BNP or NT-proBNP was consistent with HF . Echocardiographic evidence of HF was defined as meeting at least 1 of the following criteria, based on the lowest values seen on echocardiogram within 1 month of incident HF diagnosis: (1) left ventricular ejection fraction <50; (2) wall motion abnormalities; (3) left ventricular systolic dysfunction  as the presentation of HF, SSc (in which 66.7% of HF cases were adjudicated as HFpEF) and Pso (60.0%) had the highest proportion of HFpEF, whereas only 38.0% of non-CID controls with HF had HFpEF.We adjudicated HF events in a large cohort of CID patients and controls and identified significant differences in adjudicated HF subtypes across CIDs. This represents the first study to our knowledge that individually adjudicated HF events and phenotypes in a cohort examining patients with a spectrum of CIDs.We observed that isolated right-sided HF was much more common in SSc than in any other CID, and that left ventricular systolic dysfunction was more common in HIV and SLE. There was no significant difference in the rate of isolated left-sided HF across the spectrum of CIDs, however. Our findings substantiate previously postulated , 30, 31 Although these findings yield interesting CID-specific insights into HF presentation and, perhaps, underlying pathophysiologies, they require confirmation in larger, multi-center studies as one of the limitations of our current work is the relatively small sample size. Such analyses would offer the benefit of providing CID-specific insights into HF risk and pathophysiology.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Northwestern University IRB. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.DU, AS, and MF constituted the team that conceptualized the project, collected and reviewed the data, and wrote and edited the final manuscript. AR assisted with statistical analyses. All authors contributed to the article and approved the submitted version.This study was supported by the National Institutes of Health R01 HL 156592 (to MF).MF was employed by Consultant/Advisory Board, Novartis AG. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


We aimed to assess the clinical value of multimodal photoacoustic/ultrasound (PA/US) articular imaging scores, a novel imaging method which can reflect the micro-vessels and oxygenation level of inflamed joints of rheumatoid arthritis (RA).2) values of the inflamed joints were measured and classified into 3 PA+SO2 patterns. The correlations between the PA/US imaging scores and the disease activity scores were assessed.Seven small joints were examined by the PA/US imaging system. A 0–3 scoring system was used to semi-quantify the PA and power-Doppler (PD) signals, and the sums of PA and PD scores (PA-sum and PD-sum scores) of the seven joints were calculated. The relative oxygen saturation , which were superior to the PD-sum . For the patients with high PA-sum scores, significant differences between hypoxia and hyperoxia were identified in pain visual analog score (p = 0.020) and patient’s global assessment (p = 0.026). The PA+SO2 patterns presented moderate and high correlation with PGA  and VAS pain score .Thirty-one patients of RA and a total of 217 joints were examined using the PA/US system. The PA-sum had high positive correlations with the standard clinical scores of RA  contains supplementary material, which is available to authorized users. Rheumatoid arthritis (RA) is a chronic, autoimmune disease marked by symmetrical arthritis that usually involves synovial joints and causes further erosive changes and joint deformities , 2. At pNoninvasive imaging methods, including ultrasound (US) and magnetic resonance imaging, are commonly used for the evaluation of joint inflammation . As a coPhotoacoustic imaging (PAI), a hot spot of medical imaging, has broad clinical applications in identifying a variety of different diseases, including thyroid nodules , breast The feasibility of PAI in detecting minor inflammatory lesions in RA joints has been validated by previous studies, in which dual-modality PA/US imaging systems were used –25. In t2) values of lesions with different disease activity measurements of RA and to evaluate the potential value of multimodality PA/US imaging of RA in clinical practice.In this study, we performed imaging the joints of RA patients with a multimodal PA/US imaging system that combined a light device and an ultrasonic transducer. We aimed to assess the correlation of multimodal PA/US articular imaging scores and relative oxygen saturation  . Written informed consent was received from all recruited patients.RA patients aged older than 18 years old were recruited from the outpatient clinic of rheumatology at PUMCH from December 2018 to October 2019. The patients were diagnosed with RA according to the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria. Patients complicated with other types of arthritis, including osteoarthritis (OA), psoriatic arthritis (ReA), and gouty arthritis, were excluded.The schematic of the dual-modality imaging system is presented in Fig. A seven-joint ultrasound scoring system (US7) proposed by Backhaus et al  was utilThe semi-quantitative scoring system scored on a scale of 0–3 proposed by Szkudlarek et al  for PDUS2 values of the inflamed region were determined. The patients were divided into hyperoxic and hypoxic subgroups according to the distribution of the relative SO2 values. After calculating the SO2 values, the SO2 value and the PA-sum score were incorporated as a new index for RA patients, named the “PA+SO2 pattern.” The patients with PA-sum scores < 3 were considered to have minimal PA signals, and those with PA scores ≥ 3 were considered to have evident PA signals. According to the PA-sum scores and SO2 values, all the patients were divided into 3 groups: pattern 1, no or minimal PA signals; pattern 2, evident PA signals and hyperoxia; and pattern 3, evident PA signals and hypoxia. The associations of the PA+SO2 patterns and clinical scores were also evaluated. Detailed explanations of the identification of PA+SO2 patterns are presented in Supplementary Data SBy calculating the ratio of the pixels of the PA signals in the target areas at wavelengths of 750 nm and 830 nm, the relative SOThe relevant clinical information was recorded, including age, sex, disease duration from onset and from diagnosis confirmation, duration of morning stiffness, symptoms, and current medications. The laboratory parameters of the patients were collected, such as the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-cyclic citrullinated peptide (anti-CCP) antibodies, and rheumatoid factor (RF). For each patient, 28 joints  were clinically assessed for swelling and tenderness (the swollen joint count (SJC) and the tender joint count (TJC)) by a rheumatologist with 18 years of experience in clinical rheumatology. The visual analog scale (VAS) scores of joint pain and the patient global activity (PGA), evaluator global activity (EGA), disease activity score in 28 joints (DAS28), clinical disease activity index (CDAI), and simplified disease activity index (SDAI) values were also obtained.2 patterns) and clinical scores were evaluated by Spearman’s rank-order correlation (ρ: Spearman’s rank correlation coefficient) , p < 0.0001), DAS28 (CRP) , SDAI , and CDAI , which were all superior to the PD-sum . The PA-sum presented high positive correlations with TJC and SJC , respectively). The PD-sum had moderate to high correlations with TJC and SJC . The PA-sum had moderate positive correlation with CRP ; and the PD-sum had low positive correlation with CRP . Neither the PD-sum nor the PA-sum correlated with ESR. The PA-sum scores had moderate correlation with the patient’s VAS pain score , of which the correlation coefficient was higher than that of the PD-sum . The PA-sum had low correlation with global assessment , while the PD-sum scores were not correlated with PGA. The fitted curves of the PD/PA scoring results and clinical scores are shown in Fig. The correlations among the PA-sum scores, PD-sum scores, and RA disease activity measurements are listed in Table 2 values were calculated for a total of 21 patients with evident PA signals. The 10 cases who had no detectable PA signals within inflamed tissues with a PA-sum of 0 were excluded for measurement of SO2. The SO2 value of the small joints was 87.5 ± 10.1%. The patients were divided into the hyperoxic subgroup and the hypoxic subgroup according to the distribution of the relative SO2 values. Twelve patients were classified as hyperoxia with the relative SO2 value greater than 90%, and nine patients were hypoxia with the value smaller than 85% (Supplementary Data Sp = 0.020) and PGA (p = 0.026) were detected between patients with evident PA signals and those who were classified as hypoxic and hyperoxic (patterns 2 and 3). No differences could be identified in the other indexes among patients. The PA+SO2 patterns presented high positive correlation with VAS pain score  and moderate correlation with PGA  . Therefore, PAI may be able to accurately reflect the disease activity of the individual patients, which is especially useful for active lesions that are difficult to recognize by PDUS.We performed an overall imaging evaluation of small joints in patients with RA, including the MCP, PIP, MTP, and wrist, using a 0–3 PDUS grading scale and the simplified US7 scoring system as a reference , 31. The2) measurements of RA patients have also been performed using arthroscopy and ion electrodes by Ursula Fearo et al, but the method was relatively time-consuming and invasive [2 values, identified from pixels of PA signals. We found that, among the joints with higher levels of PA signals, the hypoxic individuals were more likely to have higher VAS and PGA scores than the hyperoxic patients. A high positive correlation was validated between the combined PA+SO2 patterns and pain VAS, and moderate correlation of PA+SO2 patterns and PGA scores, indicating that the oxygenation status might be related with the pain severity of the joints. The relative SO2 value could be used as a supplementary to assessing joint symptoms. No significant differences were detected between the PA+SO2 pattern and the other indexes. This result was not strong enough to establish the role of oxygenation in evaluating disease activity, which might be caused by the limited cases enrolled in this preliminary study. Studies about measuring oxygenation using PAI with larger sample size are required for further verifying the value of dual-wavelength PA in evaluating RA.Hypoxia has been believed to be a hallmark of inflammatory diseases in this decade, and RA is no exception . In vivoinvasive . In this2 scoring system in our study was created using built-in software, with reference to the widely approved 0–3 PD scores and US7 scoring systems, thus providing a concise and systematic evaluation of RA patients that could be more convenient and acceptable for clinicians.The multimodal PA/US system developed by our team integrated the PA modality into a high-end commercial US unit, making it possible to display real-time multimodal imaging and provide versatile imaging information for target lesions. A handheld probe combining the emission of lasers and ultrasonic waves and reception of US and PA signals was also equipped with the system, making the system easy for radiologists to operate. In addition, the PA and SO2 in the diagnosis of RA. Second, this study is a preliminary cross-sectional observational study of the multimodal PA/US imaging system, and whether these PA measures can predict treatment response and risk of RA relapse remains to be explored by a prospective cohort study in the future.There still exist several limitations in our study. First, the sample of RA patients was still small, and more patients must be recruited for further validation. Further clinical studies with larger sample sizes are also expected to explore the value of SO2 was also related with clinical scores that reflect pain severity. The multimodal PA/US imaging system provided comprehensive imaging parameters and might have great potential in the evaluation of disease activity of RA patients.The correlations between PA scores of micro-vessels and standard clinical scores for RA were identified, and relative SOESM 1(DOCX 51 kb)


Emerging evidence suggests that epicardial fat thickness (EFT) may be a critical feature to understand cardiac health and determine the risk of heart failure. The current review critically assesses and discusses evidence on the efficiency of measuring EFT, in comparison to the well-known markers B-type natriuretic peptide (BNP) and its N-terminal fragment pro-B-type natriuretic peptide (NT-proBNP), as a prognostic and diagnostic approach in individuals with or at risk of heart failure. A systematic approach was undertaken to search major databases, PubMed, Scopus, Google Scholar and the Cochrane library to identify studies that quantified EFT and serum BNP/NT-proBNP levels in individuals with or at risk of heart failure. Twelve studies met the inclusion criteria and a total of 1983 participants were included in this systematic review. Evidence shows a clear association between increased EFT and elevated BNP/NT-proBNP levels in individuals with metabolic disease and suggests that both methods can be used for heart failure diagnosis and prognosis. However, due to the broad spectrum of challenges linked with measuring EFT, BNP/Pro-BNP is the predominant method used for heart failure diagnosis and prognosis in clinical practice. Nonetheless, measuring EFT provides a powerful and reproducible diagnostic tool for risk stratification and heart failure diagnosis and prognosis. Importantly, measuring EFT proves valuable to validate BNP/NT-proBNP levels to predict heart failure, especially due to its non-invasive nature.The online version contains supplementary material available at 10.1007/s10741-021-10160-3. Heart failure results from structural and functional defects in the myocardium which lead to impaired ventricular filling or ejection of blood into circulation. While the central element of heart failure may be ventricular dysfunction, other prominent defects include abnormalities in the pericardium, endocardium, as well as heart valves and major vessels , 2. ThesVarious biomarkers have been identified depending on their pathophysiological impact on cardiomyocytes. These include biomarkers of systemic inflammation, oxidative stress, myocardial stress, myocardial injury, neurohormones and renal function . NatriurThere is no difference in the predictive accuracy of BNP and NT-proBNP and both peptides independently predict heart failure outcome , 14, altIn recent years, a growing number of studies have provided evidence that epicardial fat thickness (EFT) plays an important role in the development and progression of heart failure. Echocardiography of EFT has contributed to understanding the relationship between epicardial adipose tissue (EAT) and the underlying myocardial defects that confer heart failure . LipotoxTaken together, these findings indicate that measuring both EFT and BNP/NT-proBNP may offer increased sensitivity and predictive ability of clinical outcomes, including mortality and rehospitalization. Consequently, measuring EFT, in combination with assessing serum biomarkers like BNP/NT-proBNP, may serve as potential prognostic tools in heart failure patients and aid to identify patients at increased risk of heart failure. The present systematic review aims to critically assess and discuss studies that measured EFT and serum BNP/NT-proBNP levels as a diagnostic and prognostic approach in individuals with or at risk of heart failure. Importantly, this review will report on the efficiency of determining the levels of BNP/NT-proBNP in correlation with EFT to classify individuals with or at risk of heart failure.A search of articles indexed in electronic databases PubMed, Scopus, Google Scholar and Cochrane library between date of inception and 10 February 2021 was conducted. The search terms included the medical subject heading (MeSH) term “B-type natriuretic peptide” and keywords “epicardial adipose tissue” “epicardial fat thickness” as well as corresponding terms. References were managed and duplicate studies removed in Mendeley (version 1.1.18). The titles and abstracts of the articles from the electronic search outputs were screened independently by two reviewers (TAN and TMN) to identify eligible studies, while a third reviewer (PVD) was consulted for adjudication when required. Full-text copies of eligible articles were retrieved and reviewed by two independent reviewers (TAN and TMN) for inclusion, while discrepancies were resolved by a third reviewer (PVD).Question 1: Are EFT and BNP/NT-proBNP levels diagnostic or prognostic markers of heart failure?Question 2: Is EFT and BNP/NT-proBNP differentially regulated in individuals with or at-risk of heart failure?The systematic review included studies reporting EFT and serum levels of BNP/NT-proBNP in individuals with or at risk of heart failure. Only articles reporting primary findings were included, while reviews and letters were excluded. Review articles were screened to identify studies that may have been missed using our search strategy. This systematic review was conducted to answer the following questions:Participants: Individuals with heart failure or individuals with an increased risk of developing heart failure such as those with cardiometabolic diseases.Exposure: No intervention was used in this study.Comparator: Individuals without overt heart failure and/or at risk of heart failure.Outcome: EFT and BNP/NT-proBNP levels.This was achieved using the following:k) statistics tool. The kappa scores can range from − 1 to + 1, where 0 represents the amount of agreement that can be expected from random chance, and 1 represents perfect agreement between the reviewers. Kappa values ≤ 0 indicates no agreement, 0.01–0.20 as none to slight, 0.21–0.40 as fair, 0.41– 0.60 as moderate, 0.61–0.80 as substantial and 0.81–1.00 as almost perfect agreement.Data were independently extracted and tabulated in Microsoft Excel based on study details , characteristics of population  and measurements of EFT and BNP/NT-proBNP. Two reviewers (TAN and SXH) independently appraised the study quality and risk of bias using the Newcastle–Ottawa Scale, which is appropriate for cross-sectional and case–control studies . The cheA total of 15 studies were identified from the search strategy, and of these, 12 studies reported on the association between EFT and serum levels of BNP/NT-proBNP in patients with heart failure or individuals at risk of heart failure. Studies were excluded if they were reviews , not avan = 1071) and six studies reported on EFT and BNP/NT-proBNP levels in patients at risk of heart failure (n = 912). Participants at risk for heart failure had Cushing’s syndrome, obesity, coronary artery disease (CAD), non-ischemic dilated cardiomyopathy (NIDCP), acute ischemic stroke (AIS) and systematic sclerosis (SSc). Five studies were conducted in Turkey and one each in Greece, Norway, China, Spain, Netherland, the USA, and Italy. The study designs were cross-sectional (n = 1) and case control (n = 11). Ten studies were conducted in adults with an age range of 49.4 ± 8.4 to 71.4 ± 11 years, while two studies were conducted in children with ages ranging between 10.46 ± 2.38 and 14.3 ± 1.7 years.Of the 12 included articles, six studies reported on EFT and BNP/NT-proBNP levels in heart failure patients , perfect agreement for comparability with 100% agreement  and an agreement equal to chance for the outcome with 50% agreement . An overview of the quality assessment scores can be found in the supplementary file The quality of the 12 included studies ranged from unsatisfactory to good with numerical scores ranging from 6 to 10 and a median score of 8. Two studies scored as very good, seven studies scored as good, two studies were scored as satisfactory and one study scored unsatisfactory. The inter-rater reliability of all the domains was assessed using Cohen’s kappa. The agreement was scored as substantial agreement for the selection of participants with 75% agreement  risk and subsequent heart failure. Thus, it remains essential to identify potential diagnostic features such as EFT, in conjunction with elevated BNP levels to detect risk of heart failure in patients with comorbidities. Six studies reported EFT and BNP/NT-proBNP levels in patients with diseases associated with metabolic dysfunction Table .Table 2ABassareo and colleagues demonstrated that patients with Cushing’s syndrome may present with an increased risk of heart failure as they display significantly higher EFT, which correlates with elevated NT-proBNP levels . This reEarly detection of clinical deterioration is a critical component of heart failure management to facilitate the initiation of appropriate and effective therapeutic strategies. Heart failure is a chronic and progressive multifaceted disorder which prompts inflammation and metabolic disturbances . CardiacAlthough EAT may exert cardioprotective effects, through the secretion of anti-inflammatory adipokines and supplying energy in the form of triglycerides, an enhanced myocardial lipid supply and its oxidative capacity cause detrimental effects on the underlying myocardium , 44. FatFurthermore, evidence from the current review highlights a clear correlation between increased EFT and elevated levels of BNP/NT-proBNP in individuals with an increased risk of heart failure, particularly in the presence of illnesses such as CAD. Similar observations were identified in patients with systemic sclerosis , a condiThe summarized evidence suggests that measuring both EFT and BNP/NT-proBNP levels can be useful to classify patients with or at increased risk of heart failure. Currently, measuring BNP/NT-proBNP levels is the predominant method for heart failure prognosis and diagnosis in clinical practice due to the broad spectrum of challenges associated with EFT measurement. These challenges include difficulties in differentiating between epicardial fat and pericardial fat, undefined cut-off values for EFT which varies across disease spectrum, high costs of EFT measuring techniques compared to BNP/NT-proBNP measurements, the unavailability of resources to measure EFT in low-income countries and ethnic differences in EFT  Fig. 2)2). DespiSupplementary file1 (PDF 148 KB)Supplementary file2 (XLSX 12 KB)Below is the link to the electronic supplementary material.