Fetal MRI has played an essential role in the evaluation and management of congenital diaphragmatic hernia (CDH). We aimed to investigate whether the mediastinal shift angle (MSA) value was associated with the prognosis and the severity of left CDH and explore the relationship between the MSA value and fetal and neonatal cardiac structures and functions.From January 2012 to December 2020, the fetal MSA values of left CDH in our institution were retrospectively measured. Other prenatal parameters and clinical outcomes of them are collected. We also measured the fetal and postnatal echocardiography parameters to analyze linear correlation with MSA values.p < 0.001]. The MSA value of the high-risk defect group [CDH Study Group (CDHSG) C/D type] was significantly higher than that of the low-risk defect group . The AUC for severity was 0.766  and the best cut-off value for MSA was 30.7°. Higher MSA correlates with decreased fetal Z-score of left ventricle (LV) width, the diameter of the mitral valve (MV), peak velocity of MV and tricuspid valve (TV), and neonatal LV end-diastolic diameter (LVEDD) and velocity of tricuspid regurgitation .A total of 94 patients with left CDH were included. MSA was significantly higher in the deceased group than in the survived group [((38.3 ± 4.7)° vs. 32.3 ± 5.3)°, A high MSA value can effectively predict high-risk defects and high mortality of left CDH. The higher the MSA value, the worse the neonatal conditions, the respiratory and cardiovascular prognosis. The MSA values could reflect the level of left heart underdevelopment, including decreased dimensions and diastolic dysfunction of the left ventricle. Congenital diaphragmatic hernia (CDH) is a congenital malformation due to the diaphragm defect that permits herniation of abdominal viscera into the thoracic cavity. The incidence of CDH is ~2.6 per 10,000 live births .About 2/3 of CDH can be diagnosed on prenatal sonography in the second trimester . RecentlTypically, the displacement of the mediastinum in the left CDH is more severe than that of the right CDH. Scholars have suggested that the mediastinal shift angle (MSA) should be used as a more convenient and quick predictor of the mortality of the left CDH . HoweverThe clinical data of live births with left CDH prenatally diagnosed admitted to our institution from January 2012 to December 2020 were retrospectively analyzed. Inclusion criteria: ① Live births diagnosed with left CDH in the department of pediatric surgery; ② Fetal MRI was performed in our hospital; ③ Delivered in our hospital and transferred with intubation in PICU. Exclusion criteria: ① Poor image quality of fetal MRI due to motion artifacts or other factors impact the assessment; ② Combined with other severe cardiac malformations, lung malformations, or other congenital malformations with chromosomal abnormalities or syndromes that affect postnatal survival definitely; ③ The clinical outcome is unclear on discharge.2 value) within 1 h after birth, the degree of the diaphragm defect found during operation, etc]. According to Lally's classification criteria, the degrees of diaphragm defects are divided into four categories: A, B, C, and D, from small to large  at diagnosis, type of organ herniated on prenatal ultrasound, lung-to-head rate (LHR), observed/expected LHR (O/E LHR), mediastinal shift angle (MSA) on fetal MRI], neonatal-related parameters , the O/E LHR value was significantly lower , more herniation of liver and stomach, and GA at diagnosis was lower . Further, patients were divided into liver-up and liver-down groups with or without intrathoracic herniation of the liver. In the liver-up group, the MSA value was higher in survivors than in non-survivors (p < 0.001). There is no significant difference between survivors and non-survivors in the liver-down group ° vs. (32.3 ± 5.3), p < 0.0001). A cut-off of MSA value >33.7° had the highest value of Youden's Index, with a sensitivity to predict survival rate at the discharge of 90.00%, a specificity of 58.11%. The AUC was 0.832 for O/E LHR (95%CI: 0.733–0.906). The AUC was 0.748 for GA at diagnosis  for predicting the mortality, which was significantly better than chance  with type A diaphragm defects, 27 (32.1%) with type B defects, 29 (34.5%) with type C defects, and 5 (6.0%) with type D defects observed during CDH repair surgery. One-way ANOVA analyzed groups, and the MSA values differed significantly between the four groups (p < 0.001). There was also a statistically significant difference in GA at diagnosis between the two groups (p = 0.001), the high-risk defect group had a higher proportion of stomach herniation (p = 0.005), and no significant difference was found in liver herniation (p = 0.193). Neonatal clinical features were similar in both groups  = 1.249, p = 0.002; EXP (B) = 15.458, p = 0.012], whereas O/E LHR and GA at diagnosis were not . No statistical difference was found when comparing the AUC between MSA value and stomach herniation.When the MSA values were used to predict the severity, the AUC was 0.766 , and the longer the length of ICU stay and the length of hospital stay overall .Linear regression analysis was performed between 36 fetal echocardiographic parameters and MSA values . The medZ-score, RV width Z-score, MV Z-score, and RV/LV , and were positively correlated with MPA/AAo .In terms of fetal cardiac structure, MSA values were negatively correlated with LV width Z-score, MPA peak Z-score, MV peak Z-score and TV peak Z-score .In terms of flow velocity, negative linear correlations were found between MSA values and AAo peak p = 0.016, adjusted R2 = 0.057; p = 0.014, adjusted R2 = 0.060) and had a positive linear correlation with TR .Linear regression analysis was performed between MSA values and echocardiographic parameters of 87 neonates within 48 h after birth . We founp = 0.008, adjusted R2 = 0.094) and had a positive linear correlation with TR . The echocardiography's median days were 1.0  days postoperatively.Linear regression analysis was performed between MSA values and the parameters in the last echocardiography of 65 children . We founThere was no significant linear correlation between MSA values and LVEDD, LVESD, LVEF, FS, and TR in the last echocardiography of 62 children in stable condition at discharge. The median days of the last echocardiography before discharge was 10.0  days.This study found that fetal MRI mediastinal shift angle was one of the positive predictors of mortality in neonates with isolated left CDH. At the same time, we found that the higher the MSA value, the greater the degree of the defect from our data analysis, which leads to a more severe CDH. And it has high feasibility for prenatal assessment due to its simplicity of measurement.Due to non-invasiveness and reproducibility, prenatal ultrasound is currently applied in most institutions for prenatal diagnosis. O/E LHR, liver herniation, etc., are extensively used prenatally to predict the prognosis of CDH . HoweverRecently, fetal MRI has been gradually used for prenatal assessment of CDH . MRI andSome MRI predictors, such as observed/expected total fetal lung volume (O/E TFLV) , could aAnita Romiti et al. proposed in 2020 that the MSA could be used to predict the mortality of neonates with isolated left CDH. The AUC for predicting mortality was 0.931, and the optimal cut-off value was 38.2° . HoweverDefect size is considered the only reliable marker of neonatal mortality and morbidity . PatientWe also found that the MSA value was correlated with the 5-min Apgar score, and the blood gas analysis value within 1 h after birth. Previous studies have shown that insufficient gas exchange within 24 h after birth is a risk factor for CDH neonates , suggestPrevious studies have found high RV pressure overload caused by elevated pulmonary artery pressure could result in persistent mechanical compression of the left heart, preventing lateral growth of LV . BesidesReduced MV and TV peak velocity suggest ventricle diastolic dysfunction. The decrease of the main pulmonary artery and aorta flow velocity can be related to pulmonary artery resistance and ventricular systolic function. Previous literature has suggested that the MSA value could insinuate the severity of LV insufficiency. There is a significant correlation between high MSA values and increased demands for sildenafil, which could reduce pulmonary hypertension, and Dopamine or Dopamine other vasoactive drugs .Our study also has some limitations. We did not examine the MRI of the same patient at different gestational weeks. So even if we believe that there is no correlation between MSA and GA of MRI, we are unable accurately know whether there is precisely a correlation.A high MSA value can effectively predict high-risk defects and high mortality of left CDH. The higher the MSA value, the worse the neonatal conditions and respiratory and cardiovascular prognosis. The MSA values could reflect the level of left heart underdevelopment, including decreased dimensions and diastolic dysfunction of the left ventricle. In the future, we will perform a further long-term follow-up of pulmonary function and cardiac function to analyze the continuous effect of MSA on cardiac and pulmonary function in children with CDH.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by XHEC-STCSM-2020-039. Written informed consent from the participants' legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements. Written informed consent was obtained from the individual(s), and minor(s)' legal guardian/next of kin, for the publication of any potentially identifiable images or data included in this article.XuW, QS, and JW contributed to the study's conception and design. XuW and QS wrote the first draft of the manuscript. XiW, ML, and WX contributed to the original data and revised the article. WWu, WWa, and WP performed the statistical analysis. All authors approved the final version of the article.This study was supported in part by grants from Shanghai Shenkang Hospital Development Center. The grant number is SHDC2020CR2063B.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.


Sports physicians and physiologists have aimed to assess exercise in young and master athletes so as to work out their conditioning levels and design training programs accordingly. Cardiopulmonary exercise testing (CPET) provides a thorough assessment of the physiologic responses of the pulmonary, cardiovascular, muscular, and cellular oxidative systems to exercise in both athletic individuals and those with cardiovascular conditions, and has been used successfully to assess post-COVID-19 infection sequelae in competitive athletes ,3.On the other hand, athletic training is known to induce morphological and functional cardiovascular adaptations of both ventricles and atria, collectively known as athlete’s heart. Apart from advanced echocardiographic methods, cardiac magnetic resonance (CMR) is an imaging modality with a high spatial resolution and no exposure to ionizing radiation, and has the benefit of tissue characterization by exploiting gadolinium-based contrast late enhancement as a marker of myocardial fibrosis. Its additional novel developments in tissue characterization, particularly in the last 5–10 years, have been increasingly used in clinical practice in pathology discrimination, particularly with inherited cardiomyopathy. These may provide an accurate diagnosis in challenging cases and may differentiate from various pathologies, but, at the same time, provide insights into atrial structure, function, and future risk of atrial and ventricular arrhythmia . More specifically, biatrial function was estimated by peak atrial longitudinal and contraction strains, before and after races in master athletes. The results of a cross-sectional study by the group of D’Ascenzi in Italy did not confirm the hypothesis of acute atrial dysfunction induced by ultra-endurance exercise, even though one athlete developed atrial fibrillation during the race . FurtherMoreover, in a single-center study, again from Switzerland, 12-lead ECG, signal-averaged ECG, 24 h Holter ECG, and advanced left atrial echocardiographic data were prospectively collected in patients with hypertrophic cardiomyopathy, hypertensive disease, and endurance athletes. Structural and electrical atrial remodeling is more advanced in hypertrophic cardiomyopathy compared to hypertensive disease and endurance athletes . AnotherLastly, and quite importantly, the Italian group from Padova by Corrado et al. has summarized important recent work on the diagnostic assessment of athletes with premature ventricular beats (PVBs) and contrast-enhanced CMR imaging. The morphology, complexity, and exercise inducibility of PVBs can help estimate the probability of an underlying heart disease. Based on these features, the CMR imaging and assessment of non-ischemic scars, as well as their patterns and extent, may be indicated even when echocardiography is normal .


The effect of chronic pulmonary regurgitation (PR) on right ventricular (RV) dysfunction in repaired Tetralogy of Fallot (RTOF) patients is well recognized by cardiac magnetic resonance (CMR). However, the link between RV wall motion, intracardiac flow and PR has not been established. Hemodynamic force (HDF) represents the global force exchanged between intracardiac blood volume and endocardium, measurable by 4D flow or by a novel mathematical model of wall motion. In our study, we used this novel methodology to derive HDF in a cohort of RTOF patients, exclusively using routine CMR imaging.RTOF patients and controls with CMR imaging were retrospectively included. Three-dimensional (3D) models of RV were segmented, including RV outflow tract (RVOT). Feature-tracking software  captured endocardial contours from long/short-axis cine and used to reconstruct RV wall motion. A global HDF vector was computed from the moving surface, then decomposed into amplitude/impulse of three directional components based on reference . HDF were compared and correlated against CMR and exercise stress test parameters. A subset of RTOF patients had 4D flow that was used to derive vorticity (for correlation) and HDF (for comparison against cine method).p<0.05). PR% correlated with Diaphragm-RVOT HDF amplitude/impulse . RV ejection fraction modestly correlated with global HDF amplitude . VO2–max correlated with Septal-to-Free Wall HDF impulse . Diaphragm-to-RVOT HDF correlated with RVOT vorticity . There was no significant measurement bias between Cine-derived HDF and 4D flow-derived HDF by Bland-Altman analysis.68 RTOF patients and 20 controls were included. RTOF patients had increased diastolic HDF amplitude in all three directions (RTOF patients have abnormal diastolic HDF that is correlated to PR, RV function, exercise capacity and vorticity. HDF can be derived from conventional cine, and is a potential link between RV wall motion and intracardiac flow from PR in RTOF patients. Tetralogy of Fallot is the most common cyanotic heart disease that is surgically managed in infancy . DespiteCMR studies utilizing three-dimensional (3D) spatial encoding combined with 3D velocity-encoded phase contrast (4D flow) have demonstrated that RTOF patients have significant alterations to intraventricular fluid dynamics in the RV. These alterations include abnormal vorticity, turbulent kinetic energy, viscous energy losses and hemodynamic forces (HDF) –8. AdditTo date, there has only been one 4D flow study specifically focused on HDF in RTOF patients by Sjöberg et al. in 19 RTOF patients . Their aThus, the purpose of this study was to derive HDF in a retrospective cohort of RTOF patients, exclusively using routine CMR imaging, and investigate the potential relationships between HDF, PR, and RV function.This was an Institutional Review Board-approved retrospective study, involving patients who underwent a CMR study between December 2018 and August 2021. RTOF patients included those with pulmonary stenosis (TOF-PS) who underwent either transannular or infundibular patch repair, as well as those with pulmonary atresia (TOF-PA) who underwent right ventricle-to-pulmonary artery (RV-PA) conduit repair. Patients with poor imaging quality or significant stent/sternal artifact were excluded. Patients with evidence of elevated pulmonary vascular resistance (confirmed by cardiac catheterization) were also excluded. For comparison, CMR datasets from normal controls were included. Normal controls included those who underwent CMR imaging for separate clinical indication  and found to have normal RV size, function and pulmonary-to-systemic flow ratio (Qp:Qs) < 1.2:1.All CMR studies were performed with a Siemens 1.5T scanner. CMR data included cine imaging (long-axis and short-axis cine), contrast-enhanced magnetic resonance angiography (MRA), three-dimensional steady state free precession imaging (3D SSFP), two-dimensional phase contrast across the pulmonary valve (venc set between 2–2.5 m/s) and 4D flow. The cine acquisition sequence parameters included FOV = 270–360 × 202–270 mm, matrix = 208–256 × 156–192, TE = 1.1–1.22 ms, flip angle = 50, slice thickness = 6–8 mm, number of segments = 9–11 or 39–48 and number of acceleration factor = 2 or 4 depending on use of breath hold or motion corrected re-binning as per lab standard . The 4D O2–max and % predicted VO2–max), O2 pulse and ventilatory efficiency (VE/VCO2–max).Standard clinical measurements of the RV, such as indexed end-diastolic/end-systolic volumes (RVEDVi/RVESVi), ejection fraction (RV-EF%), and pulmonary regurgitant fraction (PR%) were obtained. For RTOF patients, electrocardiogram and cardiopulmonary exercise stress test (CPET) results within 1 years of CMR study were also collated for QRS duration, CPET parameters, including maximal oxygen consumption  of the RV volume over the cardiac cycle.To create a continuous representation of RV motion, the data contour points from QStrain were used to compute diffeomorphic mappings  from theHistorically, HDF or the global intraventricular pressure gradient was computed by integrating the material derivative of blood flow velocity over the ventricular volume, using 4D flow data. In this work, the global HDF vector d volume . In thisS(t) is the RV surface, comprising both the endocardium and the valvular planes, ρ is the blood density , where •for healthy subjects, only the pulmonary valve plane was assumed to be open in systole (resp. diastole), and the flow rate across the open portion of the RV surface was first obtained from mass conservation, •for RTOF patients, both the tricuspid and pulmonary valve planes were assumed to be open in diastole. The flow rate across the pulmonary valve plane was directly imposed based on the one measured by two-dimensional phase-contrast, while the flow across the tricuspid valve plane was obtained from mass conservation. The velocity on both planes was computed assuming uniform unidirectional flow.The derived HDF vector was then divided by RV volume at each phase of the cardiac cycle to allow for proper comparison between subjects. It is worth noting that even if the derivation of Eq. 1 is formally exact, approximations are introduced in the actual calculations in terms of (i) reconstruction of RV kinematics; (ii) assumption of uniform and unidirectional flow at the valve orifices.The HDF vector was decomposed into three directional components based on a reference system defined by Sjöberg et al. . The ApiA number of parameters were extracted from the time profile of HDF, normalized against the instantaneous RV volume: (i) the force amplitude during diastole, computed as the root mean square, normalized by the corresponding time interval; (ii) the net impulse (area under the curve) during diastole, normalized by the corresponding time interval; (iii) the angles formed by the mean diastolic force vector with the three reference axes. The amplitude and impulse were calculated for each force component as well as for the HDF module .To validate the cine-based method for computing HDF, forces were also obtained from 4D flow datasets using the traditional approach. A segmentation mask derived from the previously described RV kinematics were used to isolate velocity vector fields within the domains of interest. After background-phase correction, the masks were further screened to remove regions of noise artifact. HDF was then calculated using the volume integral of the material time-derivative of blood velocity:and normalized against the instantaneous RV volume.4D flow quantification of vorticity in the total RV and RVOT was derived as part of a previous RTOF study . The 3D The normalized vorticity (units of 1/s) was calculated by spatially integrating the vorticity magnitude Total−Diastole, ωRVOT−Diastole) were collected for analysis.The peak values within the total RV and RVOT during diastole  RTOF patients without PVR; (#2) RTOF patients with concurrent CPET parameters and (#3) RTOF patients with concurrent 4D flow data. Correlations between continuous variables were assessed using Pearson’s correlation coefficient . Unpaired fficient . Bland-A2, age 23.4 ± 11.2 years) and twenty normal control studies  were included , with no change in Diaphragm-to-RVOT angle  or Apical-to-Basal angle .Overall comparison of diastolic HDF amplitude and impulse are summarized in The alterations in diastolic HDF are elaborated in a representative RTOF patient and control of similar size/age, as demonstrated in by r = 0.578, p < 0.0001, r = 0.508, p < 0.0001 and –0.4468, p = 0.0007, respectively), followed by Global HDF amplitude/impulse  and Apical-to-Basal HDF amplitude/impulse . RV-EF% modestly correlated with global HDF amplitude , Apical-to-Basal HDF amplitude  and Septum-to-Free Wall impulse . There were no diastolic HDF correlations with RVEDVi . QRS duration only modestly correlated with Diaphragm-RVOT Angle .Diastolic HDF correlations with RV-EF and PR% are demonstrated in 2–max and % predicted VO2–max was 28 ± 7 mL/kg/min and 72 ± 19%, respectively. There were no significant correlations between VO2–max and % predicted VO2–max with conventional CMR measurements of the RV , Septal-to-Free Wall HDF impulse  and Global HDF Impulse .Among the RTOF cohort, 24 patients had CPET performed within 1.2 ± 6.1 months of CMR study. This subgroup cohort consisted of 20 with TOF-PS and 4 with TOF-PA; 20 had transannular patch, 4 had conduit repair. The mean PR% was 32 ± 17 % and mean RV-EF% was 51 ± 7%. The mean VOf the RV . MeanwhiA total of 9 RTOF patients had follow-up CMR after PVR, as demonstrated in r = 0.407, p = 0.009) and RVOT vorticity correlated with Diaphragm-to-RVOT HDF  for Diaphragm-to-RVOT direction, 0.535 ± 0.22 (p < 0.0001) for Septal-to-Free Wall direction, and 0.776 ± 0.108 (p < 0.0001) for Apical-to-Basal direction.A total of 40 RTOF patients had 4D flow datasets for analysis and comparison. Total diastolic vorticity correlated with Apical-to-Basal HDF  Diastolic HDF of the RV can be quantified by wall motion analysis instead of 4D flow; (#2) RTOF patients have alterations to diastolic HDF, particularly along the Diaphragm-to-RVOT direction and Apical-to-Basal direction; and (#3) diastolic HDF is correlated with PR, RV dysfunction, vorticity and exercise capacity. To our knowledge, this is the first RTOF study to derive HDF exclusively from conventional CMR cine imaging.2–max or % predicted VO2–max)  .The intraventricular and deformation parameters not traditionally considered in pressure-volume analysis are pertinent to the pathophysiology of RTOF. 4D flow studies of RTOF have demonstrated unique flow and deformation patterns that are related to PR, independent of RV size , 6, 27. As a link between intracardiac flow and wall motion, HDF may have utility as an early indicator for biomechanical dysfunction in RTOF patients. Previous studies have shown that HDF represents a sensible indicator of ventricular function that may show early alterations of ventricular function . HDF anaex-vivo and in-vitro studies. In normal controls, the dominant diastolic flow in the RV is an organized, “donut”-shaped ring-vortex surrounding the tricuspid inflow, a result of longitudinal lengthening/retraction of the RV myocardium . Written informed consent from the participants or their legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.FC and Y-HL were the primary contributors to study design, analysis of CMR measurements, interpretation of results, and writing the manuscript. SK contributed to the analysis of CMR measurements and writing the manuscript. MC, PK, and JR contributed to the analysis of CMR measurements. EB, GP, and LO contributed to the study design, interpretation of results, and writing the manuscript. All authors read and approved the final manuscript.The contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Center for Advancing Translational Sciences or the National Institutes of Health.MC, PK, and JR were employed by Medis Medical Imaging Systems. 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.


Heart failure (HF) after right ventricular myocardial infarction (RVMI) is common and complicates its clinical course. This review aims to provide a current overview on the characteristic features of RV failure with focus on acute management.While HF after RVMI is classically seen after acute proximal right coronary artery occlusion, RV dysfunction may also occur after larger infarctions in the left coronary artery. Because of its different anatomy and physiology, the RV appears to be more resistant to permanent infarction compared to the LV with greater potential for recovery of ischemic myocardium. Hypotension and elevated jugular pressure in the presence of clear lung fields are hallmark signs of RV failure and should prompt confirmation by echocardiography. Management decisions are still mainly based on small studies and extrapolation of findings from LV failure. Early revascularization improves short- and long-term outcomes. Acute management should further focus on optimization of preload and afterload, maintenance of sufficient perfusion pressures, and prompt management of arrhythmias and concomitant LV failure, if present. In case of cardiogenic shock, use of vasopressors and/or inotropes should be considered along with timely use of mechanical circulatory support (MCS) in eligible patients.HF after RVMI is still a marker of worse outcome in acute coronary syndrome. Prompt revascularization, careful medical therapy with attention to the special physiology of the RV, and selected use of MCS provide the RV the time it needs to recover from the ischemic insult. Despite significant progress in the last 20 years, ischemic heart disease remains the single most common cause of death in Europe in both men and women in 2021 . This haIsolated RVMI is a rare event and only occurs in around 3% of cases . LikewisThis is due to the blood supply of the RV Fig. : The mai2 reserve that can be readily mobilized by stressors such as exercise or ischemia [Compared to the LV, the RV has lower afterload and lower wall stress in physiologic conditions as it is connected to the low pressure and high-compliance pulmonary circulation. It performs only one-fourth of the stroke work of the LV and has a wall thickness of just one-third of the LV. Resting energy expenditure of the RV is therefore significantly lower, resulting in a larger coronary Oischemia ••, 12.The lower contractile pressures of the RV allow for coronary flow in both systole and diastole as compared to the LV, where most of the flow only occurs during diastole.Autopsies in patients with proximal RCA occlusions showed that the RV is protected from significant infarction by collateral flow from the LAD through the moderator band artery . MassiveThe RV can maintain function during moderate coronary hypoperfusion, possibly because coronary blood flow can be increased and myocardial oxygen demand decreased by endogenous nitric oxide release .Interestingly, the RV appears to behave differently in response to myocardial ischemia compared to the LV with a higher chance of recovery. Several features suggest that RV dysfunction due to RVMI is more commonly mediated by ischemic stunning of viable myocardium rather than overt infarction with irreversible myocardial necrosis Fig. :ComparedIn RVMI with clinically manifest HF, these compensatory measures have failed resulting in significant RV contractile dysfunction. Depressed RV performance due to ischemia decreases the delivery of blood to the LV leading to decreased systemic cardiac output and hypotension. Indeed, hypotension is more common complication in patients with RVMI than anterior MI . IschemiThe degree and magnitude of these effects depend greatly on the presence of concomitant LV dysfunction. A significant proportion of RV systolic function is mediated by contraction of the interventricular septum leading to longitudinal shortening of the RV. Hence, RV dysfunction is aggravated when there is prior or concomitant ischemic damage in the LAD territory which supplies the apical and anteroseptal regions of the septum. In larger MIs or in patients with preexisting systolic dysfunction, it is often difficult to attribute the cause of hemodynamic instability specifically to the left or the right ventricle due to their close interplay. In these instances, invasive hemodynamic measurements, such as obtained by right heart catheterization, may be helpful.In patients with symptoms and signs of an ACS , RV infarction should be suspected in all patients who present with inferior STEMI in the conventional 12-lead electrocardiogram (ECG). ST-elevation in V1, especially if combined with ST-depression in V2, marked ST depression in V2 combined with an isoelectric ST-segment in V1 or ST elevation in III larger than II (lead III is more rightward facing than lead II) are indicators of RV infarction. Diagnosis is confirmed by obtaining a right precordial ECG. Here, ST-elevation ≥ 1 mm in V4R alone or ≥ 0.5 mm in several leads between V4R and V1 is diagnostic for acute RVMI . The preClinically, heart failure due to RVMI should be suspected when there is hypotension (± shock) and increased jugular venous pressure  in a patient with clear lung fields. Pronounced peripheral oedema, anasarca, ascites, or liver distension are uncommon in the acute phase but represent common signs of decompensation in chronic RV failure.Echocardiography can be used to further confirm the diagnosis. The complex geometry of the RV makes accurate and reproducible quantification of the RV more difficult in two-dimensional echocardiography. Diagnosis of RV dysfunction should therefore incorporate several different echocardiographic measures of RV function. These include right atrial and RV dimensions , longitudinal function as measured by tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular systolic velocity, RV fractional area change (FAC), regional wall motion abnormalities of the RV free wall, motion and displacement of the interventricular and interatrial septum, and dilatation of the inferior vena cava. The presence and degree of tricuspid regurgitation and its mechanism are also important, as are evaluation of mechanical infarct complications such as ventricular septal defects or rupture.Cardiac MRI allows more reliable and detailed quantification of RV structure and function, but is impractical in the context of acutely ill patients with HF associated with acute RVMI and thereby rarely performed.Invasive measurements using right heart catheterization are not commonly performed in the acute phase and involved with risks . When they are available, RV failure in the context of RVMI is confirmed by the combination of elevated central venous pressure (CVP ≥ 10 mmHg) and an increased CVP to pulmonary capillary wedge pressure (CVP:PCWP) ratio of > 0.8 . AdditioAs pericarditis with cardiac tamponade can present similarly, urgent echocardiography should be performed in all patients with inferior MI and hemodynamic instability to rule out this differential diagnosis. Pulmonary embolism is another important differential diagnosis, which can be hard to distinguish from RVMI. Larger pulmonary embolisms can cause significant RV strain due to the acute increase in afterload, with increased troponin and natriuretic peptides and sometimes even ST elevation in V1-V4 and even right-sided leads (i.e. V4R) , 20. HypBecause isolated RVMI with HF is rare and right ventricular HF in the context of inferior STEMI is often considered as a secondary problem, dedicated intervention studies in acute ischemic right-sided HF are rare. Management recommendations for RVMI with HF are therefore mainly based on extrapolations from animal experiments, short-term hemodynamic studies, observational evidence, and expert opinion. Therapy should address the underlying myocardial ischemia, RV preload and afterload, coronary perfusion pressure and end-organ perfusion, and potential tachyarrhythmias and bradyarrhythmias , is of great importance. In hemodynamic stable patients with STEMI or high-risk NSTEMI, revascularization should not be delayed by further diagnostic tests such as echocardiography and performed as soon as possible (“time is muscle”). Observational evidence indicates that primary PCI is associated with better outcomes in patients with RVMI with both concomitant right-sided HF or cardiogenic shock . AccordiThe healthy RV is a compliant structure that can accommodate large volume shifts by increasing contractility in response to preload. However, during ischemia, RV dilatation and diastolic dysfunction make the ventricle susceptible to both volume depletion and overload. Therefore, careful optimization of preload is important in RV failure associated with RVMI. In patients with hypotension and clinical hypoperfusion and low or normal CVP  and no signs of pulmonary oedema, an intravenous fluid challenge should be considered . Response to fluid resuscitation should be closely monitored using blood pressure and CVP. An increase in CVP > 12 mmHg (or PCWP > 15 mmHg if available) without parallel increase in blood pressure should prompt cessation of volume resuscitation. Further application of volume by increasing RV dilatation and wall stress may worsen RV ischemia and due to pericardial restraint impair cardiac output , 27, 28.Due to its thin wall and adaption to a low-pressure system, the RV is more sensitive to acute increases in afterload. An acute increase in pulmonary systolic pressure leads to a greater decline of RV stroke volume than similar increases in aortic pressure affecting LV stroke volume Fig.  28, 30••30••. InThere is only very limited evidence to guide the use of vasopressors and inotropes in RVMI with associated HF. Due to their potential of increasing myocardial oxygen consumption and arrhythmias, inotropes are particularly problematic in acute MI. Generally, their use should be limited to patients with end-organ hypoperfusion (i.e. cardiogenic shock) and attempts should be made to wean off these therapies as soon as possible ••. HowevAlternatives to dobutamine are PDE3 inhibitors such as milrinone or levosimendan  which are also known as ‘inodilators’. Because they decrease systemic vascular resistance through cAMP-mediated vasodilation, their use can be problematic in patients with right-sided HF with predominant hypotension. In a recent randomized trial in cardiogenic shock, milrinone did not show a benefit on clinical outcomes compared to dobutamine . SubgrouPatients with RVMI have a higher risk for tachyarrhythmias such as atrial fibrillation or ventricular tachycardia/fibrillation compared to anterior MIs , 44. WheRV stroke volume is relatively fixed in RV ischemia, making cardiac output more dependent on heart rate and optimal atrioventricular synchrony. Therefore, bradyarrhythmias are poorly tolerated in RVMI and should be promptly controlled. Patients with inferior STEMI are more sensitive to vagal tone in the first 24 h after infarction, possibly explaining the high incidence of sinus bradycardia at presentation. When there is evidence of increased vagal tone with significant sinus bradycardia or Mobitz type I AV block, atropine should be used first.High-degree AV block in the context of RVMI with HF is an indication for temporary cardiac pacing . It is oUse of short-term MCS has increased in cardiogenic shock in recent years. Considering the observation that RV function in RVMI often recovers over time (see chapter prognosis), MCS offers the possibility to bridge critical patients until recovery. Generally, MCS should be considered in patients with RV failure who remain in cardiogenic shock despite optimization of preload and afterload and application of vasopressors and inotropes . Good tiVenoarterial (VA)-extracorporeal membrane oxygenation (ECMO) is a practical and widely available type of short-term MCS that can be used in RV failure ••. By drRetrograde blood flow into the aorta on VA-ECMO also increases LV afterload, which in cases of biventricular failure in the setting of MI can increase RV afterload via backward failure and increased pulmonary artery pressure. Therefore, in cases of biventricular or left-dominant HF with RV involvement, additional device support to allow LV venting may sometimes be necessary such as with percutaneous microaxial flow pumps placed in the left ventricle . When RV failure predominates despite VA-ECMO, additional jugular venous cannulation  is sometimes sought to improve drainage of the RV using two venous cannulas. Data on this form of cannulation in RV failure in the setting of MI are scarce and should only be tried in selective cases when typical MCS systems have failed.While use of VA-ECMO in RV-failure is practical, system-specific complications such as differential hypoxia, limb ischemia due to arterial cannulation, bleeding, or LV strain limit its use. Dedicated systems for RV support are available such as the Impella RP® system (Abiomed Inc.) which sucks blood from the inferior vena cava and right atrium and ejects it into the main pulmonary artery using a femorally placed microaxial pump. In a small feasibility study in patients with cardiogenic shock and right-sided HF after cardiac surgery, which also included 5 patients with cardiogenic shock due to MI, invasive haemodynamics improved after Impella RP implantation with overall 30-day survival of 73% in this cohort . HoweverOther devices for temporary RV support include the TandemHeart® (Livanova Inc.), either using percutaneous arterial and venous cannulation or a dual lumen venous cannula (ProtekDuo®) or surgically implanted devices such the CentriMag® system (Abbott Laboratories). The latter allows support for up to 30 days to bridge patients to transplant, candidacy, recovery, or long-term assist devices.Chronic right-sided HF is rare after RVMI. However, when it occurs, it is associated with a worse prognosis. Evidence on disease-modifying treatments in this population are scarce. When there is concomitant systolic LV dysfunction, standard guideline-directed pharmacologic and device therapies should be used first  . CongestThe presence of RVMI based on ECG findings (ST elevation in V4R) is associated with worse prognosis in patients with inferior MI as compared to inferior MI without RV involvement . The difHowever, looking at the culprit vessel, infarction in the LAD or CX territory generally carry a higher risk of HF and mortality in both short (30 days) and long-term follow-up 5 years) compared to RCA infarctions, possibly owing to the higher risk for permanent LV dysfunction and the better potential of the RV to recover  years co.Indeed, when RV function is serially measured after first MI, the majority of patients with reduced RV function show near complete recovery over time , 54, 55.HF is a serious complication of RVMI which carries a worse short-term prognosis yet good potential for recovery. Early revascularization improves outcomes and should be a main treatment target. Careful optimization of preload and afterload, maintenance of adequate perfusion pressures, good control of arrhythmias, and atrioventricular synchrony as well as timely management of cardiogenic shock with inotropes or MCS as needed can bridge patients until the RV recovers from the ischemic insult.


To explore the value of color Doppler echocardiography (CDE) combined with serum heart-type fatty acid-binding protein (h-FABP) and cardiac troponin I (cTnI) in the diagnosis of myocardial infarction and its evaluation value in left ventricular function.  A total of 44 patients with myocardial infarction who were treated in Cangzhou Central Hospital from October 2018 to February 2020 were included in the observation group, and 45 healthy subjects were included in the control group. The serum h-FABP and cTnI levels of the two groups were compared and analyzed. The coincidence rate of echocardiography plus serum h-FABP and cTnI for single diagnosis and combined diagnosis was analyzed. The left ventricular function indexes of patients with myocardial infarction in different cardiac function grades were compared, including left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), stroke volume (SV), cardiac index (CI), and the ratio of peak velocity blood flow from left ventricular relaxation in early diastole to peak velocity flow in late diastole (E/A). The value of echocardiography combined with serum h-FABP and cTnI in the left ventricular function in patients with myocardial infarction was analyzed. P < 0.05). CDE plus serum h-FABP and cTnI was associated with significantly higher sensitivity, specificity, and accuracy in diagnosing myocardial infarction versus single detection (P < 0.05). The LVEDV, SV, and CI parameters were similar in patients with different cardiac function grades (P > 0.05). Compared with cardiac function grades I and II, the level of LVEF in patients with myocardial infarction in grades III and IV of cardiac function decreased, while the levels of LVEDD, LVESD, LVESV, and E/A increased (P < 0.05). The levels of serum h-FABP and cTnI in patients with myocardial infarction increased with the increase of cardiac function grades (P < 0.05).  The levels of serum h-FABP and cTnI in the observation group were significantly higher than those in the control group ( Patients with myocardial infarction show high levels of h-FABP and cTnI, and CDE plus the detection of serum h-FABP and cTnI levels can significantly improve the detection accuracy and effectively evaluate the left ventricular function of patients with myocardial infarction, with a certain predictive value for cardiac function grading in myocardial infarction. Acute myocardial infarction (AMI) is myocardial necrosis caused by acute and persistent ischemia and hypoxia of the coronary artery, with clinical manifestations of arrhythmia, acute circulatory dysfunction, chest pain, heart failure, and even shock, which impose a substantial threat on the life of patients , 2. PatiP > 0.05, Tables Between October 2018 and February 2020, a total of 44 patients with myocardial infarction who were treated in the Cangzhou Central Hospital were included in the observation group, and 45 healthy subjects were included in the control group. The baseline data of the observation group  years, 20 cases of inferior wall and 24 cases of anterior wall in terms of infarction site, 11 cases of grade I, 12 cases of grade II cases, 12 cases of grade III, and 9 cases of grade IV in terms of cardiac function classification) were comparable with those of the control group  years) , left ventricular end-systolic diameter (LVESD), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), stroke volume (SV), cardiac index (CI), and the ratio of peak velocity blood flow from left ventricular relaxation in early diastole to peak velocity flow in late diastole (E/A) were measured as per the guidelines of the American Society of Echocardiography.Patients in both groups were given percutaneous coronary intervention (PCI) and medication treatment. After the patients were diagnosed with AMI, they were given oral aspirin enteric tablets at an initial dose of 300 mg/d, maintained at a dose of 10 mg/d for the lifetime, and received PCI for treatment.x ± s), one-way analysis of variance was used for comparison amongst multiple groups, and the independent samples t test was used for comparison between two groups. Enumeration data were expressed as number of cases (rate), and the chi-square test was used for the comparison. Differences were considered statistically significant at P < 0.05.All data analyses were performed with SPSS 20.0 software. Measurement data were expressed as (P < 0.05).The levels of serum h-FABP and cTnI in the observation group were significantly higher than those in the control group (P < 0.05), as given in Tables The sensitivity, specificity, and accuracy of ECD combined with serum h-FABP and cTnI levels in diagnosing patients with myocardial infarction were significantly higher than those of single detection and diagnosis (P > 0.05). Compared with cardiac function grades I and II, the level of LVEF in patients with myocardial infarction in grades III and IV of cardiac function decreased, while the levels of LVEDD, LVESD, LVESV, and E/A increased (P < 0.05).The LVEDV, SV, and CI parameters were similar in patients with different cardiac function grades (P < 0.05), as given in The levels of serum h-FABP and cTnI in patients with myocardial infarction increased sequentially with the increase of cardiac function grades  was given intravenously for patients with the heart Yang deficiency type.Traditional Chinese medicine treatment of AMI can protect damaged myocardium and improve myocardial function through local relief and systemic regulation. The patients were classified into Qi deficiency and blood stasis type, Qi deficiency and phlegm stasis type, heart Qi deficiency type, and heart Yang deficiency type as per the “Criteria Related to the Diagnostic Efficacy of Chinese Medicine Evidence”  and the Patients with myocardial infarction show high levels of h-FABP and cTnI, and CDE plus the detection of serum h-FABP and cTnI levels can significantly improve the detection accuracy and effectively evaluate the left ventricular function of patients with myocardial infarction, with a certain predictive value for cardiac function grading in myocardial infarction.


Movies S1–S3). Global LV systolic function was mildly reduced. Genetic testing for HCM was negative. Cardiac magnetic resonance (middle panels and see Movies S4 and S5) and computed tomography (lower panels and see Movie S6) demonstrated that LV was divided into two chambers by an anomalous fibromuscular septum. This bundle had a synchronous movement with the LV wall and was mimicking the systo-diastolic fluctuation of the mitral valve leaflets. Papillary muscles and trabeculae were organized in a confluent manner in order to recreate a sort of mitral valve duplicate at the mid-LV level.A 37-year-old man was hospitalized in June 2021 for SARS-CoV2 pneumonia. Electrocardiogram showed repolarization abnormalities, suggestive of hypertrophic cardiomyopathy (HCM). Two-dimensional transthoracic echocardiography demonstrated hypertrophic muscle strands in the mid-apical portion of the left ventricle (LV) with increased pressure gradient at the level of mid-ventricular narrowing, this one is well depicted with the 3D method (upper panels and see Double-chambered left ventricle (DCLV) is a very rare congenital cardiac anomaly. A genetic heterogeneity was found. Type A has a superior–inferior arrangement, related to the position of the main and accessory chambers, and sometimes presents intraventricular obstruction. DCLV is usually asymptomatic. The time of occurrence and the degree of clinical symptoms are linked with the size of the orifice between the two chambers and the LV function. To our knowledge, this is the first case of DCLV with associated well-defined double mitral valve apparatus at the mid-LV level. Multimodality cardiac imaging is of pivotal importance for confirming the diagnosis of DCLV.European Heart Journal – Cardiovascular Imaging online.Conflict of interest: None declared.Funding: None declared.Data availability Data available within the article and its supplementary materials.jeac072_Supplementary_DataClick here for additional data file.


Background: Sacubitril/valsartan plays a key role in improving left ventricular remodeling and prognosis in patients with heart failure with a reduced ejection fraction (HFrEF). Moreover, some data support its role in preserving renal function. In order to better clarify the effects of sacubitril/valsartan in cardiorenal syndrome, this study evaluated its effects on the renal resistance index (RRI). Methods: A group of patients with HFrEF was enrolled. The RRI was assessed with renal echo-color Doppler at enrollment and again after at least six months of sacubitril/valsartan treatment. In a subgroup of patients, the RRI was also evaluated at least six months before enrollment. The variations in echocardiographic parameters reflecting the left and right ventricular function, as well as creatinine and the estimated glomerular filtration rate, were also evaluated. Results: After treatment with sacubitril/valsartan, significant improvements in the left ventricular ejection fraction, and a decrease in the left atrial and ventricular volumes were observed. The RRI also showed a significant decrease. No relationship was found between the improvements in the parameters reflecting cardiac function and changes in the RRI. Conclusions: Treatment with sacubitril/valsartan is associated with improvements in both left ventricular function and renal perfusion, through decreasing the renal resistance. These data help to clarify the effects of the drug on cardiorenal syndrome progression.  In patients with heart failure with a reduced left ventricular ejection fraction (HFrEF), sacubitril/valsartan has been demonstrated to be superior to ACE inhibitors (ACEi) in decreasing the risk of heart failure hospitalization and death , and in Some data have also demonstrated the ability of sacubitril/valsartan to slow the progression of renal dysfunction ,7,8,9. AIn order to better clarify the effects on the renal blood flow, the aim of this study was to evaluate the variation in the renal resistance index (RRI) after treatment with sacubitril/valsartan.We evaluated patients referred to the Heart Failure Unit of the University Policlinic Hospital of Bari from 2016 and 2019, and to the Heart Failure Unit of the University Policlinic Hospital of Foggia from 2019 and 2021 for HFrEF (ESC criteria), who had been prescribed sacubitril/valsartan. Patients from Bari were enrolled in a study aimed at evaluating the predictors of cardiorenal syndrome progression whose main results have already been published . Patient2; and serum potassium of <5.2 mmol/L. Patients taking an ACEi before study enrollment underwent a 36 h washout before the start of treatment with sacubitril/valsartan. The starting dose of sacubitril/valsartan was 24/26 mg b.i.d. or 49/51 mg b.i.d. depending on arterial pressure, renal function, and the previous ARNi/ARB dose. The dose was then up-titrated, when tolerated, to 97/103 mg b.i.d.Study design. Patients for whom sacubitril/valsartan was prescribed were evaluated. According to the indications of the Italian Ministry of Health, sacubitril/valsartan was prescribed to the patients with the New York Heart Association (NYHA) class II–IV; left ventricular ejection fraction (LVEF) of ≤ 35%; prior treatment with ACEi or angiotensin II receptor blockers (ARB) for at least 6 months; no history of angioedema; systolic arterial pressure of >95 mm Hg; estimated GFR of >30 mL/min/1.73 mBaseline evaluation (T0) was considered to be the time in which the sacubitril/valsartan therapy was started. Between 6 and 12 months after beginning ARNI, a new complete evaluation was performed (T1). Moreover, an evaluation was performed at 6 and 12 months before ARNI therapy was started (T-1). -Medical examination and ECG. Records were documented, including ischemic heart disease, arterial hypertension, diabetes mellitus, history of ventricular arrhythmic events, NYHA class, arterial pressure, heart rhythm and heart rate at ECG;-Echocardiographic examinations. Left ventricular end-diastolic volume (LVEDV), end-systolic volume (LVESV), and LVEF were calculated with Simpson’s rule. The peak of the E wave (E), through mitral pulsed Doppler at the level of the mitral leaflets, and early diastolic velocity peak (e’) at the level of the septal and lateral mitral annulus, through tissue Doppler imaging, were measured. The E/e’ ratio was then calculated as the ratio between E and the mean value of septal and lateral e’. The central venous pressure was determined through the assessment of the inferior vena cava diameter and respiratory excursion. The mitral regurgitation (MR) was evaluated and quantified in arbitrary units (a.u. range from 0 to 4). The systolic pulmonary artery pressure (PAP) was estimated by the measurement of the RV–right atrium gradient from the peak velocity of the tricuspid valve regurgitation (TR) with the simplified Bernoulli equation; this value was added to an estimate of the mean right atrium pressure. The RV systolic function was evaluated according to tricuspid annular plane systolic excursion (TAPSE);-Doppler of interlobular renal arteries. The method to assess the RRI was described previously ,13. The At T-1, T0, and T1, the following evaluations were performed:RRI is a parameter with a high inter-operator and intra-operator reproducibility, as previously demonstrated . To avoi-2) [Blood sample analyses. Blood samples were collected to evaluate NT-proBNP  and creatinine (mg/dL). The glomerular filtration rate was calculated with the abbreviated CKD-EPI formula  .Study end-points. The primary end-point of the study was to evaluate the changes in the RRI between the evaluations before and the evaluation after the introduction of sacubitril/valsartan therapy. As the secondary end-point we evaluated the changes in echocardiographic parameters after sacubitril/valsartan therapy and their relationship with those of the RRI. Reverse remodeling was defined as a relative change in LVESVI of >15% [p value of <0.05 was considered statistically significant.Statistical analysis. Continuous variables are expressed as mean values ± standard deviation. Discrete variables were summarized as frequencies and percentages. Spearman analysis was used to evaluate the relationship between the changes in the RRI and changes in the other studied parameters. To study the effect of sacubitril/valsartan therapy, we applied a linear regression mixed model on the values obtained at the different time points (before and after the therapy), with patients fitted as subject-specific random intercepts. The effects of sacubitril/valsartan therapy and the interaction at different time points were considered. If the overall effect was significant in the linear model, then pairwise differences were examined. The trends over timing points were displayed by plotting the mean values with standard error. Statistical analyses were performed in STATA software, version 12  or Statistica 6.1 software . A A total of 80 consecutive patients for whom sacubitril/valsartan was prescribed were evaluated, and 14 patients were excluded as follows: eight because of sacubitril/valsartan intolerance (seven for hypotension and one for muscular pain) and six because of a missing T1 evaluation. The clinical characteristics of the remaining 66 patients are shown in As shown in When the RRI was analyzed, a significant reduction was demonstrated after the sacubitril/valsartan treatment, whereas no differences were found between the T-1 and T0 evaluations in the 41 patients in whom it was available  (p 0.911) and E/e’ . Analogously, no correlation was found with the absolute changes in TAPSE  and PAP . In addition, the changes in the RRI were not correlated with the absolute and relative changes in creatinine  and with the relative changes in GFR . Finally, the changes in the RRI were not correlated with those of the parameters reflecting the diastolic function, i.e., LAV (Spearman’s R 0.014, The main finding of this study was that, after treatment with sacubitril/valsartan, significant improvements in renal resistances were observed and were not associated with the improvements in the left ventricular function.Sacubitril/valsartan plays a key role in the treatment of patients with HFrEF ,16. The However, the beneficial effects of sacubitril/valsartan are mediated not only by cardiac protection but also by renal protection, thus slowing the progression of cardiorenal syndrome  in patieOur results support the hypothesis that sacubitril/valsartan exerts specific nephroprotective effects that decrease arterial renal resistance and are associated with the progression of renal dysfunction. In fact, the RRI reflects arterial renal resistance ,19,20, wInterestingly, the changes in the RRI that have we observed were not related to those reflecting reverse remodeling, improvements in LVEF, or decreased left ventricular filling pressure and right pressure. As a consequence, sacubitril/valsartan might be hypothesized to have additive and direct renal effects independent from the improvements in cardiac function. Our study did not include a control group. In order to overcome this limitation and to strengthen the evidence of a causal relationship between sacubitril/valsartan therapy and RRI variation, we evaluated the parameters not only at the time of prescription and after the treatment with sacubitril/valsartan, but also at least six months before the start of the treatment. Interestingly, the RRI, as well as the left ventricular atrial and ventricular volumes and the left ventricular ejection fraction, were similar at T0 and T-1, but changed significantly after the administration of sacubitril/valsartan. These findings provide further support for the drug’s role in the observed changes.Finally, no relationship was found between the RRI changes and the changes in creatinine serum levels and estimated GFR. As previously demonstrated , an alteHowever, our study presents several limitations. It was not a randomized study, and we did not have data to compare the effects of sacubitril/valsartan with those of ACE-inhibitors or angiotensin II receptor blockers. However, all of our patients were taking one of these two classes of drugs before sacubitril/valsartan and no change was observed between T-1 and T0 evaluations, whereas the changes were observed after the initiation of sacubitril/valsartan. The changes in RRI were statistically significant but small. This could be due to the short follow-up. However, it is worth noting that no significant changes in GFR were observed during the same period. Consequently, despite the above-mentioned limitations, our results could be useful to generate hypotheses about the effects of sacubitril/valsartan on renal resistances that could occur earlier than those of GFR. Future studies should confirm our results and evaluate the RRI changes in a larger population with a longer follow-up. Sacubitril/valsartan appears to have favorable effects on arterial renal resistances and kidney function. These variations are likely to be related to the combined renal effects of the inhibition of the renin-angiotensin system and the inhibition of neprylisin. Moreover, these effects are not related to reverse remodeling, changes in creatinine serum levels, or the estimated GFR. In this sense, more evidence is needed in order to better characterize the effects on renal function and hemodynamics.


Anthracycline cardiotoxicity is a significant clinical challenge. Biomarkers to improve risk stratification and identify early cardiac injury are required.The purpose of this pilot study was to prospectively characterize anthracycline cardiotoxicity using cardiovascular magnetic resonance (CMR), echocardiography and MicroRNAs (MiRNAs), and identify baseline predictors of LVEF recovery.2 doxorubicin equivalent) were recruited and evaluated at three timepoints  with multiparametric 1.5 T CMR, echocardiography and circulating miRNAs sequencing.Twenty-four patients  with haematological malignancy scheduled to receive anthracycline chemotherapy (median dose 272 mg/m1 mapping or late gadolinium enhancement were observed.Seventeen complete datasets were obtained. CMR left ventricular ejection fraction (LVEF) fell significantly between baseline and completion of chemotherapy , before recovering significantly at 6-month follow-up . Similar results were observed for 3D echocardiography-derived LVEF and CMR-derived longitudinal, circumferential and radial feature-tracking strain. Patients were divided into tertiles according to LVEF recovery . CMR-derived mitral annular plane systolic excursion (MAPSE) was significantly different at baseline in patients exhibiting poor LVEF recovery (11.7 ± 1.5 mm) in comparison to partial recovery (13.7 ± 2.7 mm), and good recovery . Furthermore, baseline miRNA-181-5p and miRNA-221-3p expression were significantly higher in this group. T2 mapping increased significantly on completion of chemotherapy compared to baseline , but was not predictive of LVEF recovery. No changes to LV mass, extracellular volume fraction, TBaseline CMR-derived MAPSE, circulating miRNA-181-5p, and miRNA-221-3p were associated with poor recovery of LVEF 6 months after completion of anthracycline chemotherapy, suggesting their potential predictive role in this context. T2 mapping increased significantly on completion of chemotherapy but was not predictive of LVEF recovery. The study was approved by the West Midlands - Solihull Research Ethics Committee. All participants provided written informed consent.2]).The study enrolled consecutive patients age > 18 with a new diagnosis of high-grade non-Hodgkin (NHL) and Hodgkin lymphoma (HL) scheduled for ≥ 6 cycles of anthracycline, or acute myeloid leukaemia (AML) scheduled for full dose treatment with curative intent. Patients were not eligible if they had a history of prior cardiac disease or malignancy, prior chemotherapy, or had contraindications to CMR , serum biomarkers (including miRNAs and Troponin I [TnI]) and symptom enquiry were performed on the same day at three time points: prior to chemotherapy (baseline), on completion of chemotherapy, and 6 months after completion of chemotherapy. Three patients were withdrawn between baseline and completion of chemotherapy  and another four between completion of chemotherapy and 6-month follow-up 2.22.2.1Patients underwent CMR at 1.5 Tesla . Short-axis steady state free precession cines  of the left ventricle were used to measure left ventricular (LV) volumes, ejection fraction (EF) and mass by drawing epicardial and endocardial borders at end-systole and end-diastole. Measurements were indexed to body surface area, according to established methods2.2.21 map of the mid ventricular septum, on which a region of interest was drawn to determine native myocardial T1 measurements. A blood sample was taken immediately prior to CMR to determine TnI and haematocrit . The latter allowed calculation of ECV using the established formulamyocardium/ΔR1blood). Short axis mid ventricular T2 maps were obtained using a T2 prepared steady state free precession sequence , on which a region of interest was drawn to determine native myocardial T2 measurements, using Argus software .A modified look-locker inversion (MOLLI) recovery sequence2.32.3.1Echocardiograms were performed by two fully-accredited researchers using a single Epiq machine . Biplane 2D LVEF was calculated using Simpson’s rule from apical four and two chamber images and 3D LVEF using semi-automated software . Global longitudinal strain (GLS) was measured by tracing three fiducial landmarks  on the endocardial border with automated function imaging . The fidelity of contours to cardiac motion was tracked through the cardiac cycle and manually adjusted, if necessary. Measures were not recorded if there was inadequate visualization of ≥ 3 contiguous myocardial segments. MAPSE was measured in the four chamber view at the lateral mitral annulus.2.4T-wave morphology.A 12 lead surface electrocardiogram (ECG) was obtained at each study visit and assessed for abnormalities of rhythm, conduction intervals, ST and 2.5Blood was drawn at each study visit. Troponin I (TnI) was determined at the bedside . Platelet-poor plasma was prepared by drawing blood into a sodium citrate vacutainer and centrifuging at 2240 g for 10 min at room temperature. The plasma supernatant was removed to a fresh tube without disturbing the buffy coat and centrifuged again at 2240 g for 10 min at room temperature. The supernatant was removed to a fresh Eppendorf LoBind microcentrifuge tube and stored at −80 °C2.6Data from the 17 patients who completed all visits were divided into tertiles according to LVEF recovery between completion of chemotherapy and 6-month follow-up. Predictors of LVEF recovery were explored from baseline and completion of chemotherapy visits. Overall data are presented as mean ± standard deviation for continuous variables; counts and percentages for categorical variables. Paired analysis (Wilcoxon signed rank test) was used to assess temporal changes. Following rejection of a Kruskal-Wallis test, post hoc Dunn’s pairwise comparison was used in secondary analysis to explore predictors of left ventricular recovery, comparing tertiles, as defined above. Associations between variables were assessed with linear regression. Based on the available literature33.12 (range 112 to 412). Nineteen patients (79 %) received a monoclonal antibody, and fourteen (58 %) received either prednisolone or methylprednisolone during the course of their treatment.Baseline demographic data of all participants are displayed in 3.22) and completion of chemotherapy , and decreased significantly between completion of chemotherapy and 6-month follow-up , with no difference between baseline and 6-month follow-up (p = 0.89). LVEF was normal (61 ± 3 %) at baseline, decreased significantly on completion of chemotherapy , increased significantly at 6-month follow-up  but remained significantly decreased compared to baseline (p < 0.001). Mitral annular plane systolic excursion (MAPSE) decreased significantly from baseline to 6-month follow-up  and RVEF also decreased significantly between baseline (60 ± 6 %) to completion of chemotherapy . One patient met criteria for cardiotoxicity  did not change between any timepoint . IndexedAll measures of 2D feature tracking (FT) CMR strain worsened significantly on completion of chemotherapy, compared to baseline  but no other significant between-visit differences were recorded. Furthermore, neither the absolute native myocardial T2, nor the change in native myocardial T2 between baseline and completion of chemotherapy correlated with any parameters of left ventricular systolic function. No new LGE was observed during the study. Indexed left ventricular mass did not change significantly .No significant temporal changes in native myocardial The study . Native ficantly .3.3Echo-derived 2D LVEF was not significantly different across study visits. However, 3D LVEF decreased significantly between baseline and completion of chemotherapy  and increased significantly between completion of chemotherapy and 6-month follow-up , though there was no significant difference between baseline and 6-month follow-up (p = 0.81). Echo-derived GLS did not differ significantly across study visits, though there was a trend towards worsened GLS from baseline to 6-month follow-up .3.4T-wave morphology were detected during the study.One patient had ECG evidence of old anteroseptal myocardial infarction at baseline. No changes to rhythm, conduction intervals or ST segments or 3.5Troponin I increased significantly between baseline and completion of chemotherapy  but did not otherwise differ. Three patients (14 %) exhibited subclinical cardiac injury (TnI of 60.0 to 100.0 pg/ml) on completion of chemotherapy.3.6). At baseline, 91 % (22/24) of patients were NYHA class I. This had fallen to 66 % (14/21) by completion of chemotherapy and 65 % (11/17) by 6-month follow-up. Seven patients (33 %) and five patients (33 %) reported NYHA class II dyspnea at completion of chemotherapy and 6-month follow-up, respectively. One patient (6 %) was NYHA class III at 6-month follow-up.The only significant change to physiological metrics during the course of the study was that diastolic blood pressure decreased significantly between baseline and 6-month follow-up . Baseline myocardial T1 was also noted to be significantly different between tertiles, but measures were not ordinal, with tertile 2 exhibiting the highest values at baseline . No other baseline study data, nor change  between baseline and completion of chemotherapy study visits were significantly different between tertiles of LVEF recovery. Echocardiography and CMR-derived MAPSE correlated significantly (p < 0.001) but baseline echocardiography-derived MAPSE was not significantly associated with LVEF recovery (p = 0.32).Patients were divided into tertiles according to CMR LVEF recovery between completion of chemotherapy and 6-month follow-up . Selectebaseline . No othe). Both were expressed to a significantly higher degree in tertile 1, whose LVEF did not recover between completion of chemotherapy and 6-month follow-up. No significant dysregulation of miRNAs was detected on completion of chemotherapy according to patient groups defined by tertiles of LVEF recovery.In analysis of baseline miRNAs according to tertiles of LVEF recovery, two miRNAs were significantly dysregulated (likelihood ratio test) after FDR correction: miRNA-181-5p and miRNA-221-3p . Both we3.82 mapping elevation occurred following anthracycline treatment but was not predictive of subsequent LVEF recovery. Fourth, no changes in native myocardial T1, ECV, LGE or LV mass were recorded in our study with the caveat that only one patient met criteria for cardiotoxicity during the course of the study. Fifth, analysis of LVEF recovery by tertile revealed that CMR MAPSE was significantly different at baseline in patients exhibiting poor recovery of LVEF following completion of anthracycline. Furthermore, baseline expression of miRNA-181-5p and miRNA-221-3p was significantly higher in those with poor LVEF recovery.In this prospective, multiparametric CMR, echocardiography and blood biomarker study of anthracycline cardiotoxicity, we report five important findings. First, multiple measures of left ventricular systolic function  deteriorate significantly on completion of anthracycline treatment compared to baseline. Second, several measures of systolic function recover over the next 6 months, with only CMR LVEF, CMR MAPSE, and CMR 2D FTGLS persistently depressed. Third, native myocardial T3.8.1Commensurate with previous prospective studies of anthracycline cardiomyopathy3.8.2Our study prospectively documented anthracycline-related changes in 2D FT-strain in all three planes and as such, provides novel insight. All measures of CMR strain were significantly impaired on completion of anthracycline treatment. However, FTGCS and FTGRS were statistically comparable to baseline by the end of the study, whereas FTGLS remained persistently impaired. These data support and replicate previous work by Ong et al.3.8.32 mapping abnormalities are the earliest marker of cardiotoxicity, which manifested histopathologically as intracardiomyocyte vacuolisation2 mapping early after anthracycline chemotherapy, though their relationship to subsequent cardiac dysfunction is hampered by short duration of follow up2 mapping early after chemotherapy, with prospective evaluation confirming resolution of T2 mapping over a longer period of follow-up. However, early T2 mapping elevation was not associated with subsequent LVEF recovery, either on a grouped or individual level in our study.Recent animal data demonstrated that T1 mapping and ECV in the detection of early cardiotoxicity have been highlighted by animal1 mapping or ECV during the course of the study. This discrepancy may partly relate to the differing imaging timing and populations studied , the low incidence of cardiotoxicity, as well as the confounding effects of potent anti-inflammatory treatment  and cancer itself1 mapping and ECV. When taken in combination with a recent report of overlapping temporal variability between patients and healthy controlsThe potential role of native T3.8.4Echocardiography is the most accessible and widespread method to monitor cardiac function during anthracycline therapy3.8.5meta-analysis reported that miRNA-221 was associated with a poor overall survival in human carcinomaCirculating miRNAs regulate target gene expression and are an appealing biomarker because they are readily quantifiable, have a long half-life, and remain stable at extremes of temperature and pH. However, few human studies have examined their utility to detect anthracycline cardiotoxicity, and have reported a range of expression profilesFrom a methodological stand point, this study can also represent a model for designing future translation studies exploring both imaging and circulation blood biomarkers in this patients’ population.3.9This study intentionally recruited a homogenous cohort of patients to minimize baseline confounding factors and used specific hardware and software to collect and analyse data, which limits the external validity of the results to other populations and clinical systems. This was a pilot study, powered to detect temporal changes in LVEF and as such, secondary analysis for baseline and early predictors of LVEF recovery are to be considered exploratory and require further validation before firm conclusions can be drawn. Furthermore, small sample sizes are subject to both type I and type II errors, underscoring the need for validation by larger studies before firm conclusions can be drawn.The low incidence of cardiotoxicity and absence of major adverse cardiovascular events over a relatively short period of follow-up mean that the impact of the observed subclinical temporal changes on clinical outcomes has not been established.4In this prospective multimodality pilot study, we demonstrated several temporal multiparametric CMR, echocardiographic and serological cardiac changes in response to anthracycline chemotherapy with varying recovery of LVEF in the 6 months following completion of treatment. Baseline CMR-derived MAPSE and baseline circulating miRNA-181-5p, and −221-3p were associated with poor recovery of LVEF 6 months after completion of anthracycline chemotherapy. Pending validation by larger studies, these potential ‘predictive’ biomarkers may be a useful tool to inform individualized treatment and monitoring strategies for patients scheduled to receive anthracycline treatment.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


During the event, the patient was wearing an Apple Watch Series 6, which records a 30-sec single-channel ECG. The recording showed narrow QRS complex tachycardia of 216 bpm, and short RP interval and atrioventricular nodal reentrant tachycardia (AVNRT) was recognized. Due to the mild nature of the arrhythmia, antiarrhythmic pharmacotherapy was not initiated. The use of mobile health  devices such as wearables and health monitoring applications is now a valuable addition to routine cardiac diagnostics for patients of all ages and levels of cardiovascular risk.Cardiac arrhythmias occurring during pregnancy pose a therapeutic problem as antiarrhythmic drugs can be potentially harmful to the fetus. A 35-years-old woman in the 20 Cardiac arrhythmias occurring during pregnancy pose a therapeutic problem as antiarrhythmic drugs can be potentially harmful to the fetus. Therefore, in the presence of mild arrhythmias, antiarrhythmic drug therapy is not recommended. The use of mobile health  devices such as wearables and health monitoring applications is now a valuable addition to routine cardiac diagnostics for patients of all ages and levels of cardiovascular risk .th week of pregnancy was admitted to the Department of Cardiology due to the first episode of arrhythmia in her life. During normal activities, she developed palpitations and pre-syncope symptoms. Until now, she had no concomitant diseases and had no risk factors for cardiovascular disease. She was not taking any medications. On admission, the patient did not report any symptoms, was in good general condition, and was without any abnormalities in the physical examination. ECG showed sinus tachycardia 113 bpm, normal cardiac axis, and T-waves inversion in leads V1—V3  are, in addition to premature beats, the most common forms of arrhythmia in pregnancy. Atrioventricular recurrent tachycardia (AVNRT) predominates among PSVT. It is estimated that approximately 20% of patients with pre-pregnancy supraventricular tachycardia will exacerbate their symptoms during pregnancy.According to the 2019 guidelines for the management of patients with supraventricular tachycardia, vagal maneuvers are a first-line treatment for AVNRT during pregnancy. It is also recommended to avoid the use of antiarrhythmic drugs in pregnant women with mild symptoms or rare and short episodes of arrhythmia .Recently, watches have turned into devices that not only show the time, but provide a lot of information about life activity, sleep, and its phases, and some of them also have the function of recording a real-time electrocardiogram (ECG). By enabling patients to take their ECG recordings in situations such as palpitations or presyncopes, clinicians can increasingly review hard-to-reach arrhythmias and those occurring less often thanks to registration using a smartwatch . ResearcIn the case described above, the patient used the smartwatch ECG function when she felt palpitations. However, not all patients experience episodes of arrhythmia to benefit from the ECG recording. A good example is an atrial fibrillation, which is often asymptomatic. Measuring the heart rate, but also detecting cardiac arrhythmias basically uses two different technologies: photoplethysmography (PPG) and electrocardiography. The resulting pulse wave sequences can be analyzed with the help of special algorithms (their regularity and irregularity), and arrhythmias can be detected using the variability of the pulse frequency. This information is analyzed by numerous available applications designed for this purpose . A numbeNowadays, when health awareness and the need to control it increases, more and more mHealth devices appear on the market. Smartphones and smartwatches are the most popular, but that's not all. One of the most interesting proposals is Google Glass, a gadget worn on the head, which is equipped with an accelerometer, gyroscope, and a camera, thanks to which we can get to know our heart rate (HR) and respiratory rate (RR). Another noteworthy invention is Plaster Zio. It is a waterproof patch applied to the left chest that provides a single-lead ECG and is used for continuous heart rhythm monitoring. The patch can be worn for up to 14 days and provides relatively long-term heart rate monitoring without the need to replace the battery or recharge, and includes an event marker button that can be pressed when a patient experiences symptoms , 10. AnoCurrent devices can monitor ECG, heart rate, arrhythmia, blood pressure, stress, respiratory rate, temperature, saturation, ischemia, and apnea. A comparison of the most popular devices used for mobile rhythm monitoring is presented in Measurement of HR during exercise and rest can be used to predict the risk of cardiovascular disease. In healthy populations, high resting HR is associated with an increased risk of coronary artery disease and is an unfavorable predictor of outcomes in patients with established heart failure . DisturbA prolonged QT interval can predispose patients to life-threatening arrhythmias. The single-lead ECG patch BodyGuardian  and the algorithm-predicted QTc from the KardiaMobile 6-lead ECG compared to the 12-lead ECG confirmed the satisfactory quality of this type of measurements , 16. HypMobile applications for patients are very numerous and popular, which makes our phone a personal caregiver nowadays. Among the cardiological applications, the most popular are heart rate monitoring systems that simultaneously create history and graphs of the pulse wave. Some of them are related to algorithms for selecting/classifying ECG or other measurable symptoms of heart disease. In addition, you can also find programs for cardiac rehabilitation, blood pressure measurement, and systems for detecting heart failure. Other categories with a large number of cardiac applications include ECG education and interpretation, cardiology journals, calculators, and cardiopulmonary resuscitation (CPR) instructions .Considering the potential of mHealth devices, the most important thing now would be to design a unified (at the beginning even within a given country) application that would enable direct data transfer to a doctor, for instance, when the patient's state of well-being has deteriorated.Mobile devices have been conquering the world for several years. Recognizing their potential, the companies producing them try to meet customer requirements and the possibility of using them, for example in medicine. Despite the excellent results of research in this area, there are many problems that need to be solved in order to take advantage of their potential on a large scale. Barriers include heterogeneity in an application, lack of reimbursement structures, and socio-economic and demographic disproportions in access to technology. It is obvious that the devices mentioned above are most often used by young people who care about their health. Low-income people and older people will be less likely to access these tools, even though they are the group most likely to use them. When a patient uses mHealth devices, despite the diagnosis of arrhythmia by the application, there is no telemedicine network sufficiently built to send the results, such as ECG, to the doctor for evaluation. Some patients ignore the reports as irrelevant or are afraid of the diagnosis and initiation of chronic treatment . On the It usually takes months to register arrhythmias on the basis of multiple ECG recordings and frequent admissions to emergency departments . More imThe original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.Written informed consent was obtained from the participant/s for the publication of this case report.MH, GS, and EL contributed to the conception and design of the study. MH wrote the first draft of the manuscript. MH, GS, EL, and DK wrote sections of the manuscript. All authors contributed to manuscript revision, read, 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.