Accurate assessment of right atrial pressure (RAP) and pulmonary artery systolic pressure (PASP) is critical in the management of heart transplant recipients. The accuracy of echocardiography in estimating these pressures has been debated.To assess the correlation and agreement between echocardiographic estimations of right heart pressures with those of respective invasive hemodynamic measurements by right heart catheterization (RHC) in adult heart transplant recipients.This is a prospective evaluation of 84 unique measurements from heart transplant recipients who underwent RHC followed by standard echocardiographic evaluation within 159 ± 64 min with no intervening medication changes. The relationship between noninvasive pressure estimations and invasive hemodynamic measurements was examined.p = .7), and no significant agreement between these two variables (weighted kappa = −0.1). There was a modest correlation between echocardiographic estimation of PASP and invasive PASP . Bland‐Altman analysis showed a mean bias of 2.1 ± 9 mmHg (limits of agreement = −15 to 20 mmHg).Mean RAP was 7 ± 5 mmHg and mean PASP was 33 ± 8 mmHg by RHC. There was no significant correlation between echocardiographic estimation of RAP and invasive RAP (Spearman's rho = −0.05, In heart transplant recipients, there is no significant correlation or agreement between echocardiographic RAP estimation and invasively determined RAP. Noninvasive PASP estimation correlates significantly but modestly with invasively measured PASP. Further refinement of echocardiographic methods for assessment of RAP is warranted in this unique patient population. ASEAmerican Society of EchocardiographyIVCinferior vena cavaPASPpulmonary artery systolic pressureRAPright atrial pressureRHCright heart catheterizationTRtricuspid regurgitationTTEtransthoracic echocardiogram1Right atrial and pulmonary artery systolic pressures  have significant clinical implications in the diagnosis, management, and prognosis of cardiac and pulmonary disorders.2Adult heart transplant recipients who were referred for RHC and transthoracic echocardiogram (TTE) on the same day at Tufts Medical Center as part of their standard clinical treatment plan were identified and approached for participation in the study. Patients were enrolled in the study from June 2018 to May 2019. Exclusion criteria included mechanical ventilation, pulmonic stenosis, concurrent left heart catheterization, or inability to provide informed consent. All patients provided written informed consent before enrollment in the study. This study was approved by the Tufts Medical Center Institutional Review Board.Patients underwent RHC via jugular or femoral venous access. RAP, right ventricular systolic and diastolic pressures, PASP and pulmonary artery diastolic pressure, and pulmonary capillary wedge pressure were obtained, with zero‐reference level set at the midthoracic level.All patients then underwent TTE following RHC, to avoid any confounding effects of moderate sedation on hemodynamic values. All structural and functional chamber assessments were made according to the American Society of Echocardiography (ASE) guidelines.Continuous variables are expressed as mean ± standard deviation, and categorical variables as proportions. Spearman's rho or Pearson correlation coefficient was used to evaluate the association between echocardiographic estimations and invasive hemodynamic measurements by RHC, and weighted kappa and Bland‐Altman analysis3A total of 84 serial hemodynamic and echocardiographic evaluations in heart transplant recipients were included in the data analysis. Patients underwent TTE 159 ± 64 min after RHC with no intervening medication changes. Patients were 54 ± 11 years of age at the time of evaluation, and were 193 ± 294 days from cardiac transplantation (range: 4–2593 days). Forty‐eight (57%) of the patients were male. Additional basic demographic, anthropometric, hemodynamic, and echocardiographic data are provided in Table p = .7; Figure r = .08, p = .47, Figure r = −0.02, p = .86, Figure IVC assessment was not feasible in 10 patients due to suboptimal echocardiographic windows and poor visualization of the IVC. Mean RAP was 7 ± 5 mmHg (range: 1–22 mmHg) by RHC. There was no significant correlation between echocardiographic estimation of RAP and invasive RAP  was 0.18 (95% CI: 0.7–0.32), specificity of echocardiographic estimation of high RAP (>5 mmHg) was 0.59 (95% CI: 0.41–0.76), and accuracy of echocardiographic estimation of RAP was 0.38 (95% CI: 0.27–0.51).r = .39, p = .002; Figure r = .4223, p = .0003, Figure Accurate PASP estimation was not feasible in 16 patients due to lack of sufficient TR jet. Mean PASP was 33 ± 8 mmHg (range: 15–63 mmHg) by RHC. There was a modest correlation between echocardiographic estimation of PASP and invasive PASP  association between TR gradient measured by Doppler echocardiography and invasively measured PASP may possibly be due to suboptimal alignment of the continuous wave Doppler beam with TR flow to obtain maximum TR jet velocity. Further, the lack of significant correlation between estimated RAP by echocardiography and invasively measured RAP suggests that the addition of estimated RAP to the modified Bernoulli equation to obtain an estimation of the PASP only amplifies the error in estimating PASP using echocardiography.Our finding that echocardiographic estimation of RAP does not accurately predict actual RAP is perhaps not surprising given multiple conflicting prior reports.The inaccuracy of echocardiography in estimating RAP specifically in heart transplant recipients may also be related to the currently practiced surgical technique of heart transplantation. In orthotopic heart transplantation with bicaval and left atrial anastomoses, there is total excision of the recipient's right atrium, and the donor's heart implantation is performed using bicaval end‐to‐end anastomoses as well as left atrial anastomosis.Our study findings have important clinical implications. Extensive prior evidence demonstrates the diagnostic and prognostic value of RAP and PASP in diverse patient populations, thus accurate measurement of these parameters is crucial in these clinical settings. RAP provides important information about a patient's overall volume status. Elevated central venous pressure is associated with poor outcomes and prolonged treatment in critical care settings, and is correlated with impaired renal function and all‐cause mortality in patients with a wide spectrum of cardiovascular diseases.Timely and accurate assessment of RAP and PASP is especially critical in heart transplant recipients. Right ventricular dysfunction remains prevalent in heart transplant recipients, may require the use of mechanical circulatory support, and if unrecognized in a timely manner may result in fatal outcomes.There are several limitations to the present study. First, the current study only included a modest number of patients from a single heart transplant center. Second, while we tried to minimize the time lag between RHC and TTE, noninvasive estimation of intracardiac pressures were not done simultaneously at the time of invasive hemodynamic measurements due to logistical constraints and to optimize image quality during TTE. However, no intervening medication changes were made in the time between the right heart invasive hemodynamic measurements and the echocardiogram, thereby lessening the likelihood of major changes in hemodynamics during that time interval. Additionally, we used the minimum end‐inspiratory IVC diameter during spontaneous respiration rather than a sniff maneuver. The analysis was performed with this approach to preserve the image acquisition plane, to minimize any error in IVC size measurement due to movement, as well as to avoid variation in technique between patients, some of whom may not be able to perform a sniff maneuver.In conclusion, echocardiography does not accurately estimate RAP and only modestly estimates PASP in adult heart transplant recipients. Further research is needed in identifying accurate noninvasive indicators of RAP in this special patient population.


Novel Methods to Advance Diagnostic and Treatment Value of Medical Imaging for Cardiovascular Disease, focuses on tools that augment the power of medical imaging to provide detailed quantification of cardiovascular disease. Here, we present a Research Topic of 21 research articles that provide the reader with information regarding recent advancements in medical imaging improving diagnosis, prediction, monitoring, and treatment of cardiovascular disease.The use of medical imaging has substantially increased over the past decade, thanks to the technological advancements evident from the dramatic improvement in the sensitivity and spatial resolution of imaging modalities. Cardiovascular imaging has been at a crossroads regarding technological advances, with a shift in focus from single-modality diagnosis to an integrated multimodality approach that can provide comprehensive assessments of morphology, pathophysiology, and disease biology to stratify the patient risk and guide therapies. The wide inter-subject variability in cardiovascular anatomy and pathophysiology urges the design of personalized patient management, which can highly benefit from clinical imaging technologies. The remarkable advances in medical imaging have sparked the development of new image processing algorithms and image-based simulation tools. In addition to providing comprehensive diagnostic information, some tools can even predict intervention outcomes, thereby enabling personalized intervention planning. This Research Topic, De Nisco et al. confirmed the validity of swine-specific computational models to characterize coronary hemodynamics parameters and diseases such as atherosclerosis and their translation to human vascular disease. This validation was performed using a comparative computational fluid dynamics analysis (CFD) between swine-specific and human-specific models. The analysis involved several flow and anatomical features obtained through intravascular ultrasound and coronary computed tomography angiography.Accurate coronary blood flow quantification is crucial in the proper diagnosis and treatment planning in patients with coronary artery disease. Swine animal models are invaluable to study coronary flow and develop predictive tools for disease initiation and progression. Coronary hemodynamics play a fundamental role in these processes but the correspondence between human and swine coronary flow has not been previously demonstrated. Hair et al. investigated the importance of using both patient-specific anatomic and flow information from magnetic resonance angiography in order to accurately assess the functional significance of coronary lesions. The purpose of the study was to investigate the effects of varying coronary flow reserve values on the calculation of fractional flow reserve. State-of-the-art CFD analyses of coronary flow are performed on high-resolution patient-specific coronary anatomies from CT but use flow rates obtained from population statistics and allosteric scaling as inlet boundary conditions. The authors demonstrated that this approach provides fractional flow reserve values that differ from those calculated by CFD with patient-specific flow rates derived from magnetic resonance angiography data, demonstrating the importance of patient-specific features on coronary disease evaluation.A study by Blanken et al. developed a framework which quantifies coronary flow using accelerated 4D flow MRI with respiratory motion correction compressed sensing image reconstruction. The developed framework improves upon the current use of 2D flow MRI which is limited in clinical applicability. The proposed framework allows for diastolic quantification of left coronary flow which agrees with 2D flow MRI. Current intravascular ultrasound (IVUS) parameters cannot accurately diagnose intermediate coronary stenosis. By integrating IVUS parameters with lesion length, Li et al. demonstrated the potential for accurate diagnosis of intermediate coronary stenosis using IVUS parameters.Several studies have been performed which build upon current diagnostic imaging modalities. Dang et al. investigated the correlation between the quality of pericoronary adipose tissue (PCAT) derived from dual-layer spectral detector CT (SDCT) and the severity of coronary artery disease. PCAT is a known contributor to the development of atherosclerosis and the authors of this study suggest that the use of SDCT for PCAT may be an important feature to monitor in the development of coronary artery disease.Baiocchi et al. explored the effects of different imaging modalities, namely Doppler echocardiography and computed tomography, on a previously developed framework which diagnoses and monitors complex ventricular, vascular, and valvular disease for patients who undergo transcatheter aortic valve replacement (TAVR). Both of the mentioned imaging modalities along with the developed framework were compared against cardiac catheterization for patients with complex valvular, vascular, and ventricular disease who undergo TAVR in both pre and post-intervention. Schmid et al. investigated whether global indices of ventricular function measured by cardiac MRI pre-TAVR predict post-implantation outcomes. Magnetic resonance was right performed pre-TAVR to quantify volumetric function and global longitudinal and circumferential strain of both ventricles. The results of this study demonstrated that right ventricular function may play a role in predicting intermediate-term mortality in TAVR patients.Due to the wide range of differences in cardiovascular anatomy and pathophysiology, treatment planning for patients requiring valve repair or replacement calls for patient-specific approaches. Dabiri et al. developed a near real-time, machine learning framework to predict the outcomes of MitraClip (MC) intervention for mitral regurgitation. Currently, fluid structure interaction simulations are used to predict outcomes of MC interventions, however, the high computational cost of these simulations make them unpractical in clinical settings. The machine learning method proposed in this study leverages patient-specific image data including 3D echocardiographic images, which are augmented using tools like principal component analysis to ultimately obtain stress maps and mitral regurgitation through the valve, enabling to predict the outcome of MC interventions in near real time.Yu et al. adapted computational biomechanical models to study the impact of PVR with five band insertions. Using CMR images, 147 computational bi-ventricle models were constructed to simulate right ventricle cardiac functions and identify optimal band treatment options. The results from this study showed great potential of using active contraction bands to improve ventricular function in patients with Tetralogy of Fallot.Tetralogy of Fallot is a congenital heart defect which involves ventricular septal defect, pulmonary valve stenosis, aorta overriding, and right ventricular hypertrophy. Currently, this congenital disease is often surgically treated with pulmonary valve replacement (PVR) which carries risk as an open-heart operation. De Marinis and Obrist developed a data assimilation methodology which can be used to improve spatial and temporal resolution of voxel-based flow data as obtained from biomedical imaging modalities. Combined with a CFD solver, this framework can be enhance the resolution of fine-scale flow features of cardiovascular flows.Vascular disease in general is often onset due to abnormal interactions between vessel morphology and hemodynamics. Salmasi et al. investigated the impacts of blood flow patterns on the material properties of ascending thoracic aortic aneurysms from vascular remodeling. This was achieved by using image-based computational modelling to determine wall shear stresses along with ex-vivo measurements of tissue-derived mechanical and microstructural properties using segmental analysis.Saitta et al. explored the interactions between aortic morphology and hemodynamics in the development of type B aortic dissection (TBAD). Four patients with varying type B aortic dissection morphologies underwent both CT and 4D flow MRI imaging to perform flow visualization and quantitative analysis in the true and false lumens of the dissected aorta. This study demonstrated the clinical feasibility of 4D flow MRI in TBAD patients and its importance in assessing the hemodynamic footprint of this condition.An additional study by Lekavich et al. studied the effects of aerobic training compared to resistance training on cardiac and peripheral arterial capacity on cardiopulmonary and peripheral vascular function. Several parameters including strain-based variables, brachial artery flow-mediated dilation, as well as peak VO2 and peak O2 pulse were analyzed in sedentary and obese adults. The results of this study can lead to optimal choice of exercise modality to achieve specific clinical endpoints.Schollenberger et al. used arterial spin labeling MRI to solve this challenge in order to simulate cerebral hemodynamics in a patient-specific manner for patients suffering from cerebrovascular stenoses.A crucial portion of the vascular system lies within the cranium to supply the brain with adequate oxygen. Image-based CFD analysis provides precise predictions of cerebral flow when supplied with inflow-outflow boundary conditions. However, the redundancy of flow paths offered by the circle of Willis makes it difficult to establish accurate patient-specific boundary conditions from anatomical images alone. Huang et al. investigated alterations in left ventricular myocardial workload using the left ventricular pressure-strain loops in patients with type 2 diabetes mellitus. In this study, various biomechanical features including global longitudinal strain, global work index, global constructive work, and left ventricular ejection fraction were evaluated. Patient specific parameters were measured using echocardiography, 2-D speckle tracking echocardiography (STE), and LV pressure strain-loop (LVPSL) technology.Myocardial and ventricular disease have major implications on the entire cardiovascular system and must be treated promptly and properly in order to provide the best outcome for each patient. Kotronias et al. investigated the use of angiography-derived index of microcirculatory resistance to predict microvascular injury in patients with ST-segment-elevation MI. Current use of pressure-wire based methods to predict microvascular injury remain costly and procedurally complex. Peng et al. reviewed magnetic resonance texture analysis in MI, summarizing the outstanding challenges and clinical applications and illustrating how image-based metrics are increasingly used as biomarkers in the diagnosis and prognosis of cardiovascular diseases.Myocardial infarction (MI) is caused by a lack of oxygen supplied to the myocardial cells and is a major cause of death and disability worldwide Sun et al. used both 2-D and 3-D STE to evaluate myocardial strain as well as determine which method is a more robust predictor of myocardial fibrosis in heart transplant recipients. This was accomplished by evaluating myocardial fibrosis by CMR extracellular volume fraction and its association with myocardial strain, measured using the methods originally mentioned. The results of this study demonstrated the potential of both 2-D and 3-D STE to monitor the development of fibrotic remodeling following heart transplant. An additional study performed by Cui et al. used the non-invasive LVPSL method to measure global myocardial work indices in patients with dilated cardiomyopathy. The results of the study demonstrated that the parameters measured by non-invasive LVPSL can be significant predictors of myocardial fibrosis in patients with dilated cardiomyopathy.Medical imaging of myocardial fibrosis, which is associated with impaired contractility, increased stiffness, and electrophysiological alterations, is receiving increasing attention in recent years. A study performed by Kim et al., who studied patients with paroxysmal atrial fibrillation (PAF) and normal LV function imaged in sinus rhythm. The authors found LV blood particles take longer to transit the LV in PAF patients when compared to controls, suggesting that LV flow could be a sensitive biomarker that can detect subtle phenotypic differences.The idea of LV flow as a biomarker was explored using 4-D flow MRI by Morita et al., can be heavily influenced based on genetic testing. Genetic testing carries socioeconomical and psychological burdens and it is therefore important to identify patients with cardiomyopathy who are more likely to have a positive genotype. The model developed in this study demonstrates superior accuracy to predict positive genotypes in patients with cardiomyopathy compared to standard methods. The developed framework involves a deep convolutional neural network algorithm to analyze echocardiographic images.Cardiomyopathy, as shown by in silico modelling. Such models have assisted researchers in gaining a deeper and more complete understanding of cardiovascular diseases and are beginning to assist clinicians in determining personalized and optimal treatments. Moving forward, one of the major challenges in cardiovascular modelling, covering not only fluid dynamics but also electrophysiological modelling for long term patient specific predictions. As the technology develops, researchers and physicians should envision the ultimate objective of a personalized cardiovascular model that incorporates personalized genomics, cellular behavior, tissue structure integrated with cardiovascular mechanics and fluid dynamics. We hope that our readers find the work published here both informative and stimulating in the endeavor to progress the therapy of cardiovascular disease.In the past 2 decades, the use of medical imaging has drastically increased, and medical imaging had astonishing advancements. Due to the increasing focus on personalized healthcare and the devastating effect of cardiovascular diseases, there has been rising interest in the field of patient-specific image-based cardiovascular


Portopulmonary hypertension (POPH) is characterized by portal hypertension leading to splanchnic vasodilatation and formation of portosystemic shunts. These phenomena contribute directly to a decrease in peripheral vascular resistance, which is exacerbated by vasoactive substances able to bypass the liver through the portosystemic shunts, ultimately leading to a hyperdynamic state.Journal of Clinical Ultrasound Elçioğlu et al evaluate whether echocardiographic measurement of pulmonary artery stiffness (PAS) is elevated in cirrhosis patients and whether it is correlated with RV function.n = 52) and age and sex matched healthy controls (n = 59) underwent transthoracic echocardiography. Besides conventional measurements, the PAS was determined by measuring pulmonary artery flow approximately 1 cm distal to the pulmonary valve from a parasternal short axis view and dividing the maximal frequency shift by pulmonary acceleration time. In cirrhosis patients, RV fractional area change was lower than in controls (45.31 ± 3.85% vs. 49.66 ± 3.62%), while tricuspid annular plane systolic excursion was not different. Both RV and right atrial diameter were higher in cirrhosis patients, suggesting that the right heart was volume‐overloaded, pressure‐overloaded or both. Estimated sPAP (27.69 ± 3.91 vs. 23.37 ± 3.81 mmHg) and PAS (20.52 ± 6.52 vs. 13.73 ± 2.05 kHz/s) were higher in patients and there was a weak correlation between these parameters. In addition, both showed weak correlations with RV functional parameters, especially RV fractional area change. None of the echocardiographic parameters were found to be correlated with the severity of cirrhosis (MELD or Child‐Pugh‐Turcotte scores).In this issue of the 2. With regards to the pulmonary artery, a measure of stiffness should be included (RV outflow tract acceleration time <105 ms), in addition to an early diastolic pulmonary regurgitation velocity >2.2 mm/s and pulmonary artery diameter >25 mm. PAS as evaluated in the study by Elçioğlu et al may provide additional information as it not only incorporates acceleration time, but also maximal flow velocity.Although the mean sPAP in these cirrhosis patients was well below the absolute cutoff of 50 mmHg to refer patients for catheterization,Some footnotes have to be placed regarding the current study. A relatively small, single center cohort was assessed and no information on outcome was reported. It would be of interest to study the relation between PAS and mortality or complications during or after liver transplantation. Also, the predictive value of PAS to distinguish between POPH, hyperdynamic state without elevation of PVR or no PH at all remains elusive. A cutoff for elevated PAS was not identified and the authors did not report whether patients with elevated PAS also had a sPAP above 35 mmHg. It is not possible to conclude from the descriptive data in this study whether increased PAS reflects early pulmonary vascular remodeling. Finally, there were only weak correlations between PAS and RV function and both may reflect a hyperdynamic state rather than pulmonary vascular remodeling.To conclude, PAS appears to be of interest in the screening for POPH in liver transplantation candidates. Screening needs to be improved as POPH affects outcome after liver transplantation with mortality as high as 100% in patients with mean PAP >50 mmHg and as high as 50% when mean PAP is between 35 and 50 mmHg with PVR >3 Wood units.


Patients with MIS-C can present with depressed cardiac function, but if treated, the cardiac function recovered without late onset of cardiac disease. This favorable result was independent of the severity of acute LV dysfunction.Multisystem inflammatory syndrome in children (MIS-C) is a severe hyperinflammatory disease related to SARS-CoV2 infection, with frequent cardiovascular involvement in the acute setting. The aim of the study was to evaluate the cardiac function at 6 months. Thirty-two patients diagnosed with MIS-C were enrolled and underwent advanced echocardiogram at discharge and at 6 months. According to the left ventricular ejection fraction (LVEF) at admission, the patients were divided into group A (LVEF < 45%) and group B (LVEF ≥ 45%) and the follow-up results were compared. At discharge, all patients had normal LV and RV systolic function  with normal LV diastolic function  and no significant differences at 6 months. Compared to group B, the group A patients showed a reduced, even if normal, LV global longitudinal strain at discharge (−21.1% vs. −22.6%,  Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe hyperinflammatory disease that affects pediatric patients, typically 3–6 weeks after SARS-CoV2 infection ,2. Even The disease affects many organs, cardiac involvement is one of the commonest, up to 80%, and it can influence the clinical presentation, the need for intensive care, the management, and the outcomes. Although there is not a consensus regarding the proper immunomodulatory treatment ,6, immunIn the acute phase, the cardiovascular system is generally affected by mild to moderate left ventricle (LV) systolic depression, and only one-third of patients present with severely reduced LV ejection fraction (EF < 30%). Cardiogenic or vasodilatory shock can occur in up to half of the MIS-C diagnoses. Mechanisms of myocardial dysfunction are still not clear, with some evidence of post-infective immune-mediated myocarditis  detectedUp to now, most papers describe only the acute and early follow-up myocardial function with traditional echocardiographic techniques ,13,14,15Because LV function is an important prognostic determinant of cardiopulmonary pathologies in children, there is an overall agreement around the need for further follow-up dates to understand the risk of permanent dysfunction in MIS-C. To our best knowledge, there were no published data regarding long-term cardiac outcomes of patients with MIS-C in terms of monitoring coronary artery dimensions, biventricular function, and myocardial involvement with advanced echocardiographic techniques.In this study, the cardiologic follow-up data of our previously published cohort of MIS-C patients were reported . The priThis is a retrospective, single-center study performed at the Pediatric Department of the Children’s Hospital, Vittore Buzzi, Milan. We included all children and adolescents who met the criteria of MIS-C diagnosis according to the Center for Disease Control and Prevention (CDC) , who werwww.tomtec.de/technical-docs, accessed on 1 April 2022). The LV endocardial borders were automatically traced, after the manually setting of the mitral annulus points and the apex. The trace was manually adjusted only if needed. GLS was calculated as the average of the peak systolic longitudinal strain from all LV segments from the 4-, 2-, and 3-chamber images. We considered age-dependent normal values with 95% confidence interval : 0–1 year old −18.7% , 2–9 years old −21.7% , 10–13 years old from −20% , and 14–21 years old −19.9%  [The first cardiologic evaluation was carried out before IVIG administration. LVEF was calculated with Simpson’s biplane method with Philips Affinity 70 or Vivid S5 GE Healthcare. Accordingly, to the degree of acute LV function, we divided MIS-C patients into 2 groups: group A, patients with moderate to severe depression of LVEF (LVEF < 45%), and group B, patients without or with mild signs of cardiac involvement (LVEF ≥ 45%). All patients were closely followed by the cardiologists. At discharge and at 6 months, all patients underwent standard and advanced transthoracic echocardiography, recorded with Vivid S5 GE Healthcare by a single expert pediatric cardiologist (M.G.). Standard echocardiographic measurements were made, accordingly to guidelines , includi −19.2%) . Values  −19.2%) , and the −19.2%) ,27,28,29 −19.2%) .t-test or non-parametric Wilcoxon test, comparisons between groups with independent t-test and Mann–Whitney test.Statistical analyses were performed using Stata 16 . Categorical variables are described as count and percentage; quantitative ones as mean and standard deviation (sd) if normally distributed (Shapiro–Wilks test), as median and interquartile range (IQR) otherwise. Comparisons of quantitative variables at 6 months and at discharge were made with paired p-value 0.008. Cardiac biomarkers were significantly higher in group A (troponin T 72 ng/L (40–243)) and NT-pro-BNP 14,825 ng/L ) than in group B (troponin T 22ng/L (8–49)) and NT-pro-BNP 5921 ng/L ), p-value 0.01 for both variables. All patients (100%) were treated with IVIG at the time of diagnosis. Treatment with steroids (methylprednisolone) was added for 30 patients (93.8%): 15 (46.9%) received the intermediate-high dose (10–30 mg/kg iv pulse for 3 days), and 15 (46.9%) the lower dose (2 mg/kg iv for at least 5 days), depending on the severity of the disease at the presentation, followed by gradual tapering. None of our patients received a second dose of IVIG. Low-molecular-weight heparin was prescribed for 29 patients (91%), of whom seven (22%) received a therapeutic anticoagulation dosage. All patients were discharged with low-dose aspirin and 93.8% with oral corticosteroid. A detailed discussion of the acute phase data was out of the purpose of this study, and it was previously reported in another paper [We collected 32 consecutive patients with diagnoses of MIS-C, all with positive IgG serology for SARS-CoV2. According to cardiac function, ten patients (31.25%) were included in group A with myocardial dysfunction (median LVEF 33.5% ± 7.3) and 22 (68.75%) in group B without or with only mild cardiac involvement (median LVEF 55.8% ± 6.1). Our population was uniform for the baseline characteristics, without significant differences between the groups. In the acute phase, all patients had laboratory data showing a hyperinflammatory state. C-reactive protein was elevated in all patients (median 200.8 mg/L (119.48–279.3)), with significantly higher median values for group A (283 mg/L (261–308)) compared with group B (178 mg/L (92–241)), er paper .2 (±0.37) vs. 6 months (1.22 kg/m2 (±0.37), p-value < 0.001).All patients underwent a complete cardiac evaluation within 7 days from the discharge and after 6 months. We reported a significant mean increase in BSA from discharge to 6 months follow-up . All patients had normal coronary artery diameters.p-value 0.049) and the increase in LVEF  but without difference in LV GLS .The persistence of normal values was confirmed at the 6 months follow-up without statistically significant differences among most of the echocardiographic variables. The only significant parameters were the improvement of RV s’ wave , EDV was 65.3 mL (±26.7) vs. 63.2 mL (±23.9) ; while the end-diastolic volume indexed, LV mass, and LV mass indexed reached the statistical significance (EDVi 54.1 mL/m2 (±9.4) vs. 50.8 (±6.9); LV mass 83.0 g (±34.4) vs. 77.7 g (±33.6) and LV mass/BSA 68.4 g/m2 (±13.8) vs. 63.5 g/m2 (±11.3), with p-value 0.017, 0.002, and 0.001, respectively).Interestingly, LV diameters, volumes, and masses decreased from discharge to 6 months follow-up, even with different degrees of statistical significance: EDD was 41.2 mm (±6.0) at the discharge vs. 40.1 mm (±6.0) at 6 months  even if both values were normal. The difference was no more detectable at the 6 months evaluation . There was also a slight reduction in RV systolic function measured as RVFWLS, the borderline for statistical significance . All the other parameters were comparable between the two groups both at discharge and at 6 months.MIS-C is a rare and highly severe disease that affects children previously infected by SARS-CoV2. The cardiovascular system is one of the main systems involved and it is the major determinant of the acute management and prognosis. Many reports documented a good short-term outcome, but little is known about medium- and long-term follow-ups, and to date, there is only one pediatric paper reporting 3–6-month outcomes, although without insight into the cardiologic aspects . AccordiCoronary involvement in MIS-C is highly debated, due to a significant difference in the incidence of dilation in different studies, ranging from nearly 0% up to 25% ,36,37,38A further analysis was performed by dividing the population into the two prespecified groups. The two groups were homogeneous for all the echocardiographic parameters. Very interestingly, the only significant difference was a reduced, even if normal, mean LV GLS in group A compared to group B. The difference was detectable at discharge, but no more at the medium-term follow-up. The hypothesis is that in the group with more significant cardiac involvement, some degree of systolic impairment residues at the early follow-up despite normal LVEF, but it completely recovers at the 6-month evaluation. These findings supported the concept that cardiac involvement in MIS-C is a reversible and transient condition. In our cohort, all patients, even those with acute severe cardiac involvement, completely heal in a relatively short time frame and at 6 months no residual differences between the groups can be found. The pathophysiological mechanism of cardiac dysfunction is still not completely elucidated. Although, in most cases, cardiac dysfunction seems the result of the hyperinflammatory state and the cytokine storm that cause myocardial stunning and perivascular edema, rather than a direct myocyte injury or an immune-mediated viral trigger. The hypothesis is supported by the disproportion between myocardial damage and the relatively low increase in troponin serum level, while there is a direct correlation between the severity of heart involvement and NTproBNP and inflammatory markers ,39. TrisThis theory can be supported by the relatively low percentage of positive CMR with few cases of fibrosis and LGE compared to the numbers of cardiac dysfunction, even in the early follow-up ,14,41,42Limitations. This is a single-center study, with a retrospective design and a small sample size which limit the strength of the study. Furthermore, the study did not include the advanced echocardiographic evaluation of the acute phase before the administration of the therapy. The analysis of strain at admission could have added important information, but the need to minimize exposure of the cardiologist and the use of a portable and less performing echo machine did not allow further evaluation. In addition, the clinical instability of patients often required quick evaluations, followed by intensive care and treatment. The first-line treatment with IVIG and corticosteroids allowed a quick clinical improvement and a restitutio ad integrum of the cardiac function; however, we are aware that the standard of care in MIS-C is still debated, and we cannot be sure that recovery can occur also without treatment.MIS-C is a rare and potentially fatal novel disease, in which the heart and the cardiovascular system are frequently involved. We found that despite significant cardiac dysfunction in the early stage, all the traditional and advanced echocardiographic parameters were normal at discharge and at 6 months follow-up. We described an initially lower mean value of LV GLS in the group that experienced a significant cardiac injury in the acute phase of illness, but the difference was no more detectable at the follow-up.Although patients with MIS-C myocarditis can present with severely depressed cardiac function, they completely recovered and cardiac function normalized. We did not record any late-onset of cardiac disease at the 6-month follow-up. However, longer monitoring will be necessary to provide further insight into the disease.


Aim. To assess the effect of leisure time versus vigorous long-term dynamic physical activity (PA) on carotid stiffness in normotensive versus hypertensive subjects. Methods. The study was conducted on 120 leisure-time exercisers and 120 competitive athletes. One hundred and twenty sedentary subjects served as controls. In addition, participants were classified according to whether their systolic blood pressure was ≥130 mmHg  or normal  according to the ACC/AHA 2017 definition. Carotid artery stiffness was assessed with an echo-tracking ultrasound system, using the pressure-strain elastic modulus (EP) and one-point pulse wave velocity (PWVβ) as parameters of stiffness. Results. The effect of the two levels of PA differed in the normotensives and the hypertensives. Among the normotensives, there was an ongoing, graded reduction in EP and PWVβ from the sedentary subjects to the athletes. By contrast, among the hypertensives, the lowest levels of EP and PWVβ were found among the leisure-time PA participants. EP and PWVβ did not differ between the hypertensive sedentary subjects and the athletes. A significant interaction was found between PA and BP status on EP (p = 0.03) and a borderline interaction on PWVβ (p = 0.06). In multiple regression analyses, PA was a negative predictor of EP (p = 0.001) and PWVβ (p = 0.0001). The strength of the association was weakened after the inclusion of heart rate in the models . Conclusions. These data indicate that in people with hypertension, leisure-time PA has beneficial effects on carotid artery stiffness, whereas high-intensity chronic PA provides no benefit to vascular functions. In partThe present study was a cross-sectional analysis of data collected from 2009 to 2017 . Subjectn = 120) or normal (n = 240) according to the definition of hypertension by 2017 ACC/AHA guidelines [Office brachial BP and heart rates were measured 6 times over two visits using a validated oscillometric semiautomatic sphygmomanometer on the dominant arm, in the supine position, and a quiet room . On the idelines . The proidelines ,12. Brieidelines . At leasublished .p < 0.15 in univariate analysis were entered into a multivariate linear regression, which was used to investigate the association of carotid stiffness with PA (yes or no) and heart rate, thereby controlling for confounders. To compare regression model fit, we used the Akaike Information Criteria  and Schwarz’s Bayesian Information Criterion ) [2 test or Fisher’s exact test and were presented as a percentage. Analyses were performed using a significance level of α = 0.05 (2-sided).All continuous data were normally distributed according to the Shapiro–Wilk normality test and were presented as means (±SD). Comparisons between the three groups were carried out using a two-way analysis of covariance, using the BP status and PA category as fixed factors and age, sex, BMI, diastolic BP and smoking as covariates. Variables with a log (n)) ,17. For log (n)) ,17. In alog (n)) . Categorp = 0.03). No age difference was found between the two active groups (p = 0.36). No differences in sex distribution, systolic BP and diastolic BP were found between the three groups. The prevalence of smokers was lower among the athletes than the leisure-time PA group. BMI and heart rate progressively decreased from the sedentary subjects to the athletes (The main characteristics of the study participants are shown in athletes .p < 0.03) and in the normotensives than the hypertensives (p < 0.001). However, in a two-way ANCOVA adjusted for age, sex, BMI, diastolic blood pressure and smoking, a different pattern was observed among the normotensives and the hypertensives (p < 0.001) and PA (p = 0.009) with a significant interactive effect of the two factors (p = 0.04).EP was lower in both active groups than in the sedentary subjects (tensives . In the p < 0.02) and was lower in the normotensives than the hypertensives (p < 0.001). Again, in a two-way ANCOVA, a linear relationship was found in the normotensive group, and a U-shaped relationship was found in the hypertensive participants (p = 0.001) and PA (p = 0.003) on PWVβ, with a borderline interactive effect of the two factors (p = 0.06).Similar results were found for PWVβ. PWVβ was lower in both athletes and leisure-time PA participants than in sedentary subjects (icipants . A signip = 0.001). After the inclusion of heart rate in the regression, PA remained a significant predictor of EP, but the association was weakened with a p-value = 0.04 (p < 0.001) was attenuated after adjusting for heart rate  and improved the fit of the models , was an independent predictor of EP , indicating a cross-sectional association of heart rate with arterial stiffness ,44. AccoA limitation of our study is that we used only two PA categories and could not provide a more graded relationship between the PA dose and its effects on carotid stiffness. Another major limitation is the cross-sectional nature of our study design that precludes us from making inferences on temporality. Third, we used brachial BP for the calibration of carotid diameter changes, which usually overestimates the central BP in an age-dependent manner. However, mean age was similar in the three PA groups.There is still uncertainty as to the optimal exercise regimen required to achieve the greatest benefits in terms of cardiovascular health. The data of the present study indicate that in hypertension, there is a U-shaped relationship between the PA level and carotid stiffness, suggesting that leisure-time aerobic PA is more beneficial than high-intensity PA on arterial function. A high level of chronic PA provides no benefit to vascular structure and function in people with mildly elevated BP levels and might even cause a detrimental effect in patients with more severe hypertension ,52. The


To explore the effect of dapagliflozin on the myocardial fibrosis and the levels of inflammatory factors in heart failure patients.  60 patients with T2DM who were diagnosed as acute left heart failure or acute exacerbation of chronic left heart failure in the Department of Cardiology of our hospital from November 1, 2020, to December 31, 2021, during hospitalization were the study subjects. According to the treatment regimen, they were divided into the experimental group (EG) which received dapagliflozin and conventional drugs and the control group (CG) which received conventional drugs, with 30 cases in each group to compare and analyze the clinical indicators such as myocardial fibrosis and inflammatory factors. α, IL-1β, IL-6, and hs-CRP in the two groups were decreased gradually after treatment, and the levels of TNF-α, IL-1β, IL-6, and hs-CRP in the EG were visibly lower compared with those in the CG at week 4 of treatment (P < 0.05). The cardiac function evaluation of patients showed that the levels of LVEF and LVEDD in both groups were gradually improved after treatment, with a significant difference from the fourth week. In other words, compared with the CG, the LVEF level in the EG was obviously higher (P < 0.05), the LVEDD level was distinctly lower (P < 0.05), and the levels of ST2, BNP, and MCP-1 in the EG were clearly lower at week 4 of treatment (P < 0.05) with a statistical significance in difference.  The levels of TNF- Dapagliflozin has a definite curative effect in heart failure patients with type 2 diabetes mellitus, which can effectively reduce the inflammatory response of patients and inhibit the myocardial fibrosis, and has a potential value in improving cardiac function and promoting prognosis. In recent years, diabetes mellitus has become a serious public health problem globally, which can cause vascular endothelial injury and lead to the changes of heart construction and function, and is a high risk factor for heart failure and poor prognosis , 2. TherThe criteria were as follows. (1) All patients met the diagnostic criteria of type 2 diabetes mellitus (T2DM) in the Guideline for the Prevention and Treatment of Type 2 Diabetes Mellitus in China (2017 edition)  and the The criteria were as follows: (1) patients with the diseases such as severe sepsis and acute cerebrovascular disease that could cause cardiac dysfunction; (2) female patients in pregnancy or lactation period; (3) patients with other heart diseases like severe congenital heart disease, myocarditis, and valvular heart disease; (4) patients with malignant tumor, thyroid hyperfunction, or multiple organ failure; (5) patients with acute complication of diabetes mellitus; and (6) patients with psychic cognitive impairment or language communication disorder.60 patients with T2DM who were diagnosed as acute left heart failure or acute exacerbation of chronic left heart failure in the Department of Cardiology of our hospital from November 1, 2020, to December 31, 2021, during hospitalization were the study subjects, and they were divided into the experimental group (EG) and the control group (CG) according to the treatment regimen, with 30 cases in each group. This study was in line with the criteria of ethics and morality and was adopted after discussion by the ethics committee of our hospital.Patients in the CG were treated with conventional drug treatment, that is to say, giving them antidiabetic drugs such as metformin and insulin according to the individualized situation of patients. At the same time, beta-adrenergic blockade, calcium channel blockers, diuretics, and digitalis glycosides were used for antiheart failure treatment, and the diet guidance with low glucose and low sodium was given.Patients in the EG were treated with dapagliflozin  on the basis of conventional medication regimen at a dose of 5 mg in the morning once a day.10-15 ml of venous blood was collected before entering the group with the spontaneous coagulation at room temperature for 10-20 minutes and was centrifuged for about 20 minutes (2000-3000 r/min) to carefully collect the clear supernatant and then was sent to experiment center of our hospital for inspection. The specimens were repeatedly collected at week 1 and week 4 of treatment.The general information includes age, gender, systolic pressure, heart rate, duration of diabetes mellitus, course of heart failure, NYHA grade, previous medication history, and complicationsα (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), high-sensitivity c-reactive protein (hs-CRP), soluble suppression of tumorigenicity 2 (ST2), and b-type natriuretic peptide (BNP) were detected in the department of laboratory. The level of monocyte chemoattractant protein-1 (MCP-1) in serum was detected using enzyme-linked immunosorbent assay (ELISA method)The blood was collected at admission time and at week 1 and week 4 of treatment for centrifugation to collect the clear supernatant, and the tumor necrosis factor-The ultrasound cardiography (UCG) examination was performed at admission time and week 1 and week 4 of treatment to analyze statistically the left ventricle ejection fraction (LVEF) and left ventricular end diastolic dimension (LVEDD)x2 and t-test, indicated by [n (%)] and P < 0.05, the differences were considered to be statistically significant.The software SPSS 23.0 was used for the data processing in this study to calculate the differences in data between the two groups, and GraphPad Prism 7  was used for chart production. The study data including enumeration and measurement were tested by P > 0.05). See details in The age, gender, systolic pressure, heart rate, duration of diabetes mellitus, course of heart failure, NYHA grade, previous medication history, complications, and other general information in both groups were counted, with no statistical significance between the two groups , while the levels of TNF-α, IL-1β, IL-6, and hs-CRP in the EG were significantly lower compared with the CG at week 4 of treatment (P < 0.05).According to the statistical data of inflammatory factors in P < 0.05), and the LVEDD level was distinctly lower (P < 0.05). See details in Figures The cardiac function evaluation of patients showed that the levels of LVEF and LVEDD in both groups were gradually improved after treatment with a significant difference from the fourth week. In other words, compared with the CG, the LVEF level in the EG was obviously higher (P < 0.05) with a statistical significance in difference. See details in At week 4 of treatment, the levels of ST2, BNP, and MCP-1 in the EG were obviously lower than those in the CG , such as acute myocardial infarction and severe myocarditis on the one hand, and, on the other hand, system response caused by excessive activation of neuroendocrine system, in which myocardial fibrosis is an important pathological change in the process of heart failure , 12. Theα, IL-1β, IL-6, and hs-CRP in the two groups were decreased gradually after treatment, and the levels of TNF-α, IL-1β, IL-6, and hs-CRP in the EG were obviously lower than those in the CG at week 4 of treatment (P < 0.05). The inflammatory cascade reaction mediated by neutrophil granulocyte and mononuclear macrophages is one of the common mechanisms leading to the myocardial fibrosis, which can secrete a variety of proinflammatory cytokines such as TNF-α, IL-1β, and IL-6, leading to the myocardial fibrosis. The results of this study showed that dapagliflozin can effectively inhibit the inflammatory response in heart failure patients in the short term and reduce the levels of inflammatory factors, thus alleviating myocardial fibrosis. The clinical studies have found that the clinical pharmacological mechanism of dapagliflozin in the treatment of heart failure includes the following points. (1) Dapagliflozin can effectively reduce ventricular hypertrophy and restore dilation function. (2) The apoptosis of cardiomyocytes was inhibited, thus delaying the progress of diastolic dysfunction, and the activation of mitochondrial autophagy is an important mechanism for mediating the protective mechanism produced by dapagliflozin. (3) Dapagliflozin also reduces the oxidative stress reaction through Nrf2/ARE and other pathways, so as to hinder myocardial fibrosis and ventricular hypertrophy, improve myocardial dilation function, and promote the myocardial remodeling and improvement effect of myocardial microcirculation. The cardiac function evaluation of patients showed that the levels of LVEF and LVEDD in the two groups were gradually improved after treatment, with a significant difference from the fourth week. In other words, compared with the CG, the LVEF level in the EG was obviously higher (P < 0.05), and the LVEDD level was distinctly lower (P < 0.05), which was consistent with the results of previous studies [More and more studies have shown that immune inflammatory response exerts a vital role in the process of myocardial fibrosis so that it may be a new way to improve the myocardial fibrosis by regulating the abnormal immune inflammatory response . Inflamm studies , 19, conP < 0.05) at week 4 of treatment, indicating that dapagliflozin has an obvious inhibitory effect on myocardial fibrosis in heart failure patients with type 2 diabetes mellitus. Besides reducing the blood glucose, dapagliflozin also has multiple cardiovascular protective effects and alleviates the heart failure symptoms mainly by early hemodynamic changes. The possible mechanisms are as follows. (1) The cardiovascular risk factors were improved, including reducing the BMI, blood lipid, systolic pressure, and blood uric acid level, postponing the kidney disease, and reducing the excretion of urine protein [α, IL-1β, IL-6, and MCP-1 in myocardium by the reduction of malonaldehyde and the increase of superoxide dismutase, thus inhibiting the myocardial hypertrophy and myocardial fibrosis [In this study, the levels of ST2, BNP, and MCP-1 in the EG were overtly lower than those in the CG ( protein –22. (2) fibrosis –25. (3) The shortcomings of this study were as follows. (1) Dapagliflozin may benefit heart failure patients through multiple mechanisms, but SGLT2 is not expressed in human cardiomyocytes, mainly distributed in the kidney, and it is not clear whether dapagliflozin directly affects the cardiomyocytes, which needs to be supported by a large number of experimental results. (2) In this study, the sample size is small and the long-term efficacy of patients is not tracked, and large sample studies are still needed to further clarify its clinical value. (3) At the same time, limited by the research conditions, this study lacked the study on the adverse reactions of patients after medication, so this problem should be paid attention to in the follow-up studies.In summary, dapagliflozin has a definite curative effect on heart failure patients with type 2 diabetes mellitus, which effectively reduces the levels of inflammatory factors in patients and improves the cardiac function, and further studies will help to establish a better solution for such patients.


Youden index analysis showed that a vortex duration of 8.6% of the cardiac cycle provided a 95% sensitivity and an 83% specificity to detect PH. Reliability for the measurement of vortex duration was excellent for both intra-observer ICC = 0.823 and inter-observer ICC = 0.788. Vortex duration could be a useful parameter to non-invasively estimate mPAP in patients with suspected CTEPH.Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the causes of pulmonary hypertension (PH) and requires invasive measurement of the mean pulmonary artery pressure (mPAP) during right heart catheterisation (RHC) for the diagnosis. 4D flow MRI could provide non-invasive parameters to estimate the mPAP. Twenty-five patients with suspected CTEPH underwent cardiac MRI. Mean vortex duration (%), pulmonary distensibility, right ventricular volumes and function were measured using 4D flow MRI and cine sequences, and compared with the mPAP measured by RHC. The mPAP measured during RHC was 33 ± 16 mmHg (10–66 mmHg). PH (defined as mPAP > 20 mmHg) was present in 19 of 25 patients (76%). A vortical flow was observed in all but two patients (92%) on 4D flow images, and vortex duration showed good correlation with the mPAP (r = 0.805;  Pulmonary hypertension (PH) is a haemodynamic condition defined as a resting mean pulmonary artery pressure (mPAP) above 20 mmHg, as measured by right heart catheterisation (RHC) which is the gold standard for pressure measurement . PH can In this study, we hypothesised that abnormalities of duration of vortical flow in the main pulmonary artery should be encountered on 4D flow MRI in a specific population of patients with suspected CTEPH, and could be a marker of PH. We therefore evaluated the changes in pulmonary flow on MRI in a population of patients with suspected CTEPH, and compared our results with other MRI parameters as well as with the values measured by RHC.n = 5), incomplete MR investigation (n = 8) and a delay > 6 months between cardiac MRI and RHC (n = 2). In total, 25 patients were included . The imaging protocol included cine MR balanced Steady State Free Precession (bSSFP) sequences acquired in the long axis planes of the right ventricle  and 1 vertical long axis (VLA)) and contiguous sections acquired in the short axis plane for evaluation of right ventricular function. Following parameters were used for the acquisition: temporal resolution = 20 or 40 ms according to the cardiac rhythm of the patient; TE = 1.5 ms; pixel size = 2 mm × 2 mm × 8 mm, 25 reconstructed cardiac phases, flip angle = 30°. A 2D phase contrast flow sequence was acquired on the pulmonary artery (single slice) with the following parameters: temporal resolution = 28 ms; TE = 2.5 ms; pixel size = 2 × 2 × 6 mm; flip angle = 20°; velocity encoding (venc) = 150 cm/s. Lastly, a prototype 4D phase contrast flow sequence (Work In Progress number: 785) was acquired in the oblique sagittal orientation after contrast medium injection  with the following parameters: prospective cardiac gating; 60 slices, temporal resolution of 20–40 ms (depending on patient physiology), 24 ± 5 cardiac phases, pixel size = 2 × 2 × 2 mm, 3 directions of flow quantification, venc = 150 cm/s. Flow images were acquired during free breathing using a liver dome respiratory navigator; mean duration of the sequence was 16 ± 7 min.The RHC exam was performed in a supine position with continuous monitoring of the electrocardiogram and arterial oxygen saturation using pulse oximetry (SpO2). The modified Seldinger technique was used for venous catheterisation of the femoral , basilic or cephalic vein  The Swan Ganz catheter (7F) allowed the resting haemodynamic evaluation with measurements of mPAP, pulmonary capillary wedge pressure (PCWP) and cardiac output (CO) as determined by thermodilution (TD). Left heart catheterisation with measurement of left ventricular end diastolic pressure (LVEDP), systemic arterial pressure was also routinely performed. The coronary arteries were injected only if clinically indicated. The mid-thoracic line was used for the zero-level reference. Pulmonary vascular resistance (PVR) and cardiac index (CI) were calculated with the respective formulae: PVR = (mPAP − PCWP)/CO or (mPAP − LVEDP)/CO if LVEDP was measured; CI = cardiac output/body surface area. TD was performed with 10 mL of iced, cold, sterile isotonic glucosaline solution injected in the proximal catheter’s lumen. The temperature change was recorded at the distal end of the probe with a thermistor. Measurements were performed in triplicate, and the mean value was recorded if the difference between the highest and lowest value was ≤10%. Otherwise, 2 more measurements were performed after exclusion of the highest and lowest values. The mean of those three remaining values was then calculated.2), right ventricular end systolic volume , right ventricular ejection fraction  and right ventricular cardiac index .Cine sequences were analysed with a dedicated software  and following MRI parameters were recorded: right ventricular end diastolic volume  was measured on the 2D flow sequence, the pulmonary artery distensibility, defined as the variation of surface between diastolic and systolic phase (%) was calculated, and the peak velocity in the pulmonary artery.The mean diameter of the pulmonary artery (mm) as calculated from maximal and minimum diameters on diastolic phase was recorded. Diastolic and systolic pulmonary artery cross-section area . A background phase correction was used to reconstruct the images. One operator (LC), blinded to clinical information, performed a visual analysis of all images. They considered that the vortex was present in the pulmonary artery with the appearance of a circular formation, whose axis of rotation is perpendicular to the axis of the vessel. The end of the vortex was defined as the last image showing this structure in the artery. The presence of a vortical blood flow was noted and its relative duration with respect to the whole cardiac cycle (%) was calculated. A vortical blood flow was defined as a closed concentric ring-shaped flow with the vortical blood flow’s axis of rotation being perpendicular to the pulmonary artery (PA) on visual analysis, as previously reported . A seconp value < 0.05 was considered as significant. Analyses were performed with the SPSS software .Data are presented as mean ± SD, or median (interquartile range) depending on data distribution, or percentage. Differences between continuous data were tested with the Mann–Whitney rank-sum test for two-group comparisons. Pearson correlation coefficients (r) were calculated to assess the correlation between continuous variables. Simple regression analysis test was performed between mPAP measurements by RHC and MRI-derived vortex duration for patients with a mPAP > 20 mm Hg. Comparison between mPAP values measured by RHC and those calculated from the vortex duration by the regression equation was performed by Bland–Altman analysis. A multiple regression analysis was performed between mPAP values, vortex duration and MRI parameters that were non-significantly correlated with vortex duration. Receiver operating characteristic (ROC) analysis was applied to MR calculated parameters to assess the performance of each parameter to detect patient with PH. In order to facilitate comparison with studies that used a 25 mmHg cut-off to define PH, two different cut-offs were tested to define PH (>20 mmHg and ≥25 mmHg). The DeLong test was carried out to compare the ROC curves. A Youden index was used to evaluate the sensibility and specificity of different thresholds of vortex duration for the diagnosis of PH. Inter- and intra-observer intraclass correlation coefficient (ICC) were calculated for all subjects to evaluate the reproducibility of measurement of vortex duration  and 0.896  for a PH definition threshold of >20 mmHg and ≥25 mmHg, respectively. Right ventricular volumes; RVEF, RV cardiac index, mean diameter of PA and pulmonary distensibility showed lower AUCs but no significant differences (een AUCs . Youden n = 19), vortex duration showed good correlation with the mPAP  (In patients with pulmonary hypertension defined as mPAP > 20 mmHg ( 0.0001) A. Linear 0.0001) B.p = 0.002), PCWP , RV EDV , RV ESV , RVEF , mean diameter of PA  and PA distensibility .A weaker correlation between mean vortex duration and other RHC and MR parameters was also observed: PVR , RVEF , mean diameter of pulmonary artery  and pulmonary distensibility .Several MR parameters also displayed a correlation with the mPAP but in a lesser manner than vortex duration: RV ESV  and inter-observer ICC = 0.788 . In this study, we report that patients with PH showed a vortical flow within PA on 4D MRI and that the vortex duration correlated with the mPAP as measured during RHC, suggesting that the mPAP could be non-invasively estimated by cardiac MRI. Our results confirm the potential of measuring vortex durations in patients with suspected PH in comparison to invasive measurements through RHC.The vortex duration method was first introduced by Reiter et al. who went from using a single slice with 3D velocity encoding initially , in ordeRecently, other approaches have been tested to assess PH from 4D-MRI. These schemes are looking for a relationship between PH and abnormalities on 4D flow images, but used more complex quantitative parameters (like vorticity or helicity) instead of visual analysis of vortex duration ,23,24, mThe correlation between vortex duration and mPAP which we report was not as high as reported in two different series of patients with PH (defined as pulmonary pressure ≥ 25 mmHg), with correlation coefficients of 0.94 (AUC = 1) and 0.95 (AUC = 0.994) ,17. The The study of the ROC curves shows a higher AUC for the duration of the vortex. The lack of statistical difference with the other parameters is probably due to the relatively small number of patients. Interestingly our cut-off value for vortex duration to detect a PH with mPAP ≥ 25 mmHg was 10% of the cardiac cycle , in the same range (14.3%) as previously reported . This vaSeveral explanations have been advanced to explain the formation of vortices in PH, including reduction of arterial compliance and wall shear stress, increased PVR and endothelial cell dysfunction ,29. ThesOur study has some limitations. First, the scan time for the 4D Flow sequence was relatively long. However, acceleration techniques, such as compressed sensing are emerging and will allow such sequences to fit more easily into the clinical routine ,33. SecoIn conclusion, our results show a relationship between vortex duration in the pulmonary artery and pulmonary arterial pressure, suggesting that this non-invasive parameter could be used to estimate pulmonary arterial pressure.


Introduction: Computational modeling of cardiac mechanics and hemodynamics in ischemic heart disease (IHD) is important for a better understanding of the complex relations between ischemia-induced heterogeneity of myocardial tissue properties, regional tissue mechanics, and hemodynamic pump function. We validated and applied a lumped two-compartment modeling approach for IHD integrated into the CircAdapt model of the human heart and circulation.Methods: Ischemic contractile dysfunction was simulated by subdividing a left ventricular (LV) wall segment into a hypothetical contractile and noncontractile compartment, and dysfunction severity was determined by the noncontractile volume fraction (Results: Simulation of 20% of Conclusion: We successfully used a two-compartment model for simulation of the ventricular pump and tissue mechanics in IHD. Patient-specific optimizations using regional myocardial deformation estimated the  Computational modeling of cardiac mechanics and hemodynamics in ischemic heart disease (IHD) is important for better understanding of the complex relations between ischemia-induced heterogeneity of myocardial tissue properties, regional tissue mechanics, and hemodynamic pump function. Spatially detailed three-dimensional models based on the finite element method (FEM) are most frequently used for simulation of myocardial infarction (MI) and its effects on cardiac geometry, tissue mechanics, and electrophysiology. While many studies have successfully used FEM models for investigating the pathophysiology and potential treatment of MI , complexReduced-order modeling approaches with sufficient spatial and physiological details to accurately simulate global and regional tissue mechanics are important for patient-specific simulation of MI . The CirIn this study, we presented and tested a modeling approach for MI-induced myocardial contractile dysfunction, which is integrated into the CircAdapt modeling framework. Following previous observations by A brief description of the CircAdapt model components, which are most relevant for this study, are provided as follows. For further details on the CircAdapt model, we referred to previously published validation studies . ThereafThe CircAdapt computational model of the human heart and circulation is a closed-loop lumped-parameter model that simulates beat-to-beat hemodynamics and mechanics of the heart and blood vessels . The modPassive myocardial tissue behavior is described by the parallel elastic element, which captures both extracellular and intracellular structures. Therefore, total passive stress The extracellular matrix stress Here, In a combined experimental and modeling study, Sf,act . Since tSf,act  is appliSf,act . In thisectively . Compareectively , where tThe calculated strain For the two-compartment model, the sarcomere length In line with the study of We hypothesized that acute ischemia and subsequent reperfusion could realistically be simulated by manipulation of the tive dog   and circulating biomarkers in patients with myocardial infarction) cohort. This was a prospective study on first-time MI patients, approved by the local ethics committee (METC: NL45241.041.13) and in accordance with the Declaration of Helsinki. Patients in this study were included after an acute MI, when urgent revascularization was performed. From the measured cohort, we selected patients with narrow QRS (<120 ms), who had a minimum infarct size of 10% of the LV wall mass and a minimum relative LGE percentage of 25% in at least one myocardial AHA segment.Echocardiography was performed at the baseline  and at the 6-month follow-up using a commercially available system . LV volumes and ejection fraction (EF) were acquired by Simpson’s biplane method. Focused loops of the apical four-chamber view, two-chamber view, and three-chamber view were stored for post-processing (GE EchoPAC version 203). Speckle tracking deformation imaging of the LV was performed in 18 segments according to current clinical standards while blinded to the MRI results .At a median of 6 months after primary MI, all patients underwent contrast-enhanced 1.5 Tesla cardiac magnetic resonance (CMR) imaging . LGE image acquisition was performed 15 min after administration of 0.2 ml/kg gadobutrol , using prospective ECG-gated sequences of the short axis views from the base to apex, with 5 mm slice thickness. Images were analyzed off-line using Philips ISP9 software . Using the RV insertion points to the interventricular septum as anatomical landmarks, the heart was subdivided into 16 segments according to the model of the American Heart Association (AHA) , excludi−4, meaning that within one iteration, all parameters changed by less than 1% of the width of their MC sampling domain, or a maximum number of 1000 iterations was reached.To estimate the t) = 2 ms. MSPSO was performed in MATLAB 2019a . Simulations ran in parallel on an AMD Ryzen Threadripper 3970X.The CircAdapt model used in this study has been published before in more detail . To reduConstructed ESPVRs for the one- and two-compartment simulations of LV acute regional ischemia are shown in Simulated LV pressure-segment length loops and corresponding strain patterns at the baseline , the 6 months . At the In this computational study, we used the CircAdapt model of the human heart and circulation to test the ability of a lumped two-compartment model to realistically simulate the effects of ischemia-induced contractile dysfunction on ventricular pump and myocardial tissue mechanics. The modeling approach was first evaluated on the level of global LV mechanics by constructing ESPVRs at the baseline and during acute regional ischemia using simulations with a two- and one-compartment modeling approach. Then, simulated regional strains and pressure-length loops for increasing degrees of contractile dysfunction were compared with existing gold standard myocardial deformation measurements in dogs with acute and prolonged ischemia followed by reperfusion. Finally, patient-specific optimizations were performed to estimate the noncontractile volume fraction Constructed LV ESPVRs at baseline and during acute regional ischemia using both a one- and two-compartment modeling approach demonstrated that was used ; Table 1was used . In their kECM . When ine of 20% . QualitaSimulated strain patterns and LV pressure-segment length loops for ectively , 5. Whild kECM . This reressures . Adding reported , an acutreported . The datstunning . While istunning , which aOur simulations of prolonged ischemia and subsequent reperfusion demonstrated that erfusion ; Table 3erfusion . The occerfusion . At the xpansion . HoweverThe parameter ollow-up , suggestollow-up . Increasstunning . Increasmodeling  and clinmodeling  of straimodeling  and thermodeling . From thThe experimental measurements of fterload , this asfterload . FurtherWe successfully used a two-compartment model for simulation of ventricular pump and myocardial tissue mechanics in ischemic heart disease. Patient-specific optimizations using regional myocardial deformation successfully estimated


Ischemic cardiomyopathy refers to systolic left ventricular dysfunction in the setting of obstructive coronary artery disease and represents the most common cause of heart failure worldwide. It is often the combination of an irreversible loss of viable mass following an acute myocardial infarction (AMI) with a dysfunctional, but still viable, myocardium in the context of a chronically reduced myocardial blood flow and reduced coronary reserve. Medical treatments aiming at modulating neurohumoral response and restoring blood flow to the ischemic cardiomyocytes were shown to dramatically abate the occurrence of ventricular dysfunction and adverse remodeling in ischemic cardiomyopathy.Novel therapeutic approaches, such as mechanical unloading and modulation of the inflammatory response, appear to be promising. Furthermore, the understanding of the mechanisms by which, despite optimal treatment, heart failure ensues after AMI, with or without adverse remodeling and systolic dysfunction, is a critical step in the search for novel ways to tackle heart failure risk beyond preservation of left ventricular volumes and systolic function.In this review article, we explore the principal pathophysiological mechanisms and pathways of heart failure in ischemic cardiomyopathy, therapeutic opportunities, and knowledge gaps in this area. Ischemic cardiomyopathy refers to systolic left ventricular (LV) dysfunction in the setting of obstructive coronary artery disease (CAD), and represents the most common cause of heart failure (HF) worldwide . Left veIn this review article, we explore the principal pathophysiological mechanisms and pathways of HF in ischemic cardiomyopathy, therapeutic opportunities, and knowledge gaps in this area.The infarct size following AMI is the most important predictor of LV dysfunction and remodeling after AMI , 12. LarThe degree of LV dysfunction during the acute phase of AMI is not only the result of the irreversibly myocardial loss but may be greater due to the contribution of myocardial “stunning,” regions of depressed cardiac function following the reperfusion of an occluded artery that gradually recover over the course of a days following a successful reperfusion . The undCoronary microvascular injury following the recanalization of an occluded epicardial coronary artery is another important determinant of the final infarct size, and a predictor of future adverse remodeling and outcomes , 18. ThiAll these mechanisms contribute to a worse prognosis by causing a larger infarct size, myocardial dysfunction, and adverse remodeling .After AMI, the loss of contractile myocytes and reduced stroke volume leads to LV dilatation. This phenomenon can be acutely beneficial by maintaining stroke volume through the Frank-Starling mechanism. However, the LV wall stress is proportional to the radius of the ventricular cavity and inversely correlated to LV wall thickness, as explained by Laplace law . Hence, Reduced cardiac output promotes the activation of renin–angiotensin–aldosterone system (RAAS). Angiotensin II alters gene expression contributing to myocyte growth, affects cardiac metabolism and energetics, and increases protein synthesis in both fibroblasts and myocytes, thus increasing extracellular matrix deposition and fibrosis .AMI is a trigger for the inflammatory response aimed at clearing necrotic debris, which is then followed by an anti-inflammatory reparative phase leading to myocardial scar formation. Perturbation of this balance may acutely worsen the infarct size and chronically contributes to adverse remodeling and post-AMI . While sLV dysfunction in the setting of CAD may also occur in patients without history of AMI. Repeated episodes of stunning as well as chronic low flow may induce metabolic and cellular adaptation leading to development of dedifferentiation of cardiomyocytes (hibernating myocardium) to prevent myocardial necrosis. Hibernating myocardium is viable myocardium, and therefore retains the ability to recover function upon revascularization . The mosBesides scar and stunning/hibernation, LV dysfunction in patients with CAD may also be the result of other contributing, pre-existent, or superimposed factors, such as ventricular interdependency, electromechanical desynchrony , prior scar, or other causes of cardiomyopathies  that may coexist and meaningfully contribute to LV remodeling, dysfunction, and HF syndrome.Several treatment options are currently available, and supported by strong evidence, in order to prevent or treat HF in ischemic cardiomyopathy. Prompt reperfusion of the infarct-related artery remains the mainstay treatment for AMI. As cardiomyocyte death per unit of time appears to be curvilinear with time from arterial occlusion, achievement of arterial patency in the first few hours after AMI allows for myocardial salvage and reduced infarct size, and subsequently might reduce the incidence of heart failure and other adverse outcomes , 30. ThrSubsequent management strategies focus on modulating and interrupting the mal-adaptive process that led to infarct expansion and replacement fibrosis deposition within the cardiac muscle. Contemporary state-of-the-art pharmacological treatment focuses on modulation of the renin–angiotensin–aldosterone and of beta-adrenergic receptors. Of note, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) were shown to reduce the development of myocardial fibrosis and hypertrophy, as well as LV adverse remodeling, hence reducing the onset of HF . Table 2p = 0.17), despite the trends toward lower number of events for the individual endpoints with sacubitril-valsartan . In. In64]. Pathophysiologic mechanisms leading to HF in patients with CAD may be in fact multifactorial and only partially explained by measures of LV systolic dysfunction at rest or changes in LV volumes. The acute myocardial damage is only one of the factors implicated in the determination of cardiac contractility, LV filling pressure, and cardiac output reserve. Post-infarction inflammatory, hemodynamic and neurohormonal response, chamber compliance, myocardial stiffness, cardiac pre-existing individual risk factors, and subclinical comorbidities all contribute at vary degree to determine cardiac function and decline in cardiorespiratory fitness , 67. ResIschemic cardiomyopathy is the most common cause of HF in the general population. Treatments aiming at modulating the neurohumoral response and, in selected cases, restoring blood flow to the ischemic cardiomyocytes were shown to dramatically abate the occurrence of HFrEF in ischemic cardiomyopathy. Novel therapeutic approaches, such as mechanical unloading and modulation of the inflammatory response, appear to be promising. Furthermore, the understanding of the mechanisms by which, despite optimal treatment, HF ensues after AMI, with or without adverse remodeling and systolic dysfunction, is a critical step in the search for novel ways to measure HF risk beyond preservation of LV volumes and LVEF, and for novel interventions to reduce the incidence of HF after AMI with subsequent consequences on morbidity and mortality. The scarcity of data exploring cardiac reserve and cardiorespiratory fitness following an AMI paves the way for more systematic investigations to provide novel pathophysiological insights and a better understanding of the problem.