Pulmonary hypertension is a life-threatening complication in dogs with cardiopulmonary disease. Epoprostenol, a prostacyclin analog, is an intravenous pulmonary vasodilator used for treating pulmonary hypertension in humans; however, it has not been used in veterinary medicine. This study aimed to investigate the effects of epoprostenol on cardiac function and hemodynamics in canine models of chronic pulmonary hypertension. Six laboratory-owned dogs with chronic embolic pulmonary hypertension were anesthetized and underwent right heart catheterization and echocardiography before and after administering epoprostenol, dobutamine, dopamine, and pimobendan. In this study, high doses of epoprostenol significantly decreased pulmonary and systemic vascular resistance and increased left and right ventricular function. In contrast, dobutamine and dopamine significantly increased pulmonary arterial pressure and left and right ventricular function. Pimobendan significantly increased left and right ventricular function without increasing pulmonary arterial pressure. Our results indicate that high doses of epoprostenol might help effectively treat canine pulmonary hypertension through pulmonic and systemic vasodilating effects. Catecholamines improve left and right ventricular function; however, they might worsen the pathophysiology of pulmonary hypertension. Pimobendan also improved left and right ventricular function without worsening pulmonary hypertension pathophysiology; however, a stronger vasodilating effect was observed with epoprostenol.Pulmonary hypertension (PH) is a life-threatening complication in dogs with cardiopulmonary disease. Epoprostenol is an intravenous pulmonary vasodilator used to treat PH in humans; however, its efficacy in dogs remains unknown. We investigated the cardiovascular effects of epoprostenol and several cardiac agents for acute heart failure in canine models of chronic PH. Six dogs with chronic PH were anesthetized and underwent right heart catheterization and echocardiography before and after infusion of epoprostenol, dobutamine, dopamine and pimobendane. . High-dose epoprostenol (15–20 ng/kg/min) tended to decrease pulmonary arterial pressure (PAP) while significantly decreasing pulmonary and systemic vascular resistance and increasing left and right ventricular  function. Pimobendan significantly increased LV and RV functions without increasing PAP. Conversely, dobutamine and dopamine significantly increased LV and RV function as well as PAP. This study revealed the efficacy of epoprostenol in treating canine PH through its pulmonary and systemic vasodilating effects. Although catecholamines improve LV and RV function, they might worsen PH pathophysiology, and careful monitoring may be necessary when using these drugs. Pimobendan improved LV and RV function without increasing PAP; however, a stronger vasodilating effect was observed with epoprostenol. Pulmonary hypertension (PH) is a life-threatening disease in dogs that is characterized by an increase in pulmonary arterial pressure (PAP) and/or pulmonary vascular resistance (PVR) ,2. This The American College of Veterinary Internal Medicine has recently established guidelines for diagnosing and treating PH in dogs , which h2 (prostacyclin) analog, has been used to treat PH and is the only intravenous agent highly recommended for patients with severe PH [2 analog has various effects on pulmonic and systemic hemodynamics, including the protective effect on endothelial cells, as well as pulmonary and systemic vasodilating, anti-inflammatory and anti-platelet effects [2 analog (beraprost sodium) in canine PH [In human medicine, epoprostenol, an intravenous prostaglandin Ievere PH ,8. The p effects ,11,12,13anine PH ,15. HoweThis study aimed to evaluate the clinical utility of epoprostenol for treating PH in canine models of chronic PH. Additionally, we compared the effects of epoprostenol and various cardiac drugs for acute heart failure on RV hemodynamics and function. We hypothesized that epoprostenol might be an additional treatment option for PH in dogs.This was a hypothesis-driven prospective observational study. All procedures followed the Guidelines for Institutional Laboratory Animal Care and Use of Nippon Veterinary and Life Science University in Japan, and the study was approved by the Ethics committee for Animal Use of Nippon Veterinary and Life Science University, Japan .Six male beagles owned by our laboratory  were used in this study. Chronic PH models were developed by continuous injection of 150–300 µm diameter microsphere  into peripheral pulmonary arteries via multipurpose catheter surgically placed in the main pulmonary artery  ,16,17. CAll dogs were administered ampicillin sodium . Anesthesia was induced with intravenous propofol injection  and maintained with 1.5–2.0% isoflurane  mixed with 100% oxygen. Each dog received a continuous infusion of the drugs examined in this study or lactated Ringer’s solution at a rate of 1.0 mL/kg/h throughout the study protocol. Pressure-controlled mechanical ventilation was initiated at 8–10 breaths/minute. The end-tidal partial pressure of carbon dioxide, transcutaneously measured tissue oxygen saturation, heart rate and systemic arterial pressure (SAP) obtained using the oscillometric method were monitored throughout the study protocol with a multiparameter monitor . All dogs were restrained in the left lateral recumbency. After clipping, aseptic preparation and draping around the right jugular vein, local anesthesia was induced with percutaneous injection of lidocaine around the right jugular vein. A 6-Fr sheath introducer  was inserted into the right jugular vein using the Seldinger retainment technique.After a 15-min anesthetic stabilization period, right heart catheterization and transthoracic echocardiography were performed to establish baseline data. Subsequently, epoprostenol  dissolved in a dedicated solution was infused at doses of 2, 5, 10, 15 and 20 ng/kg/min, referencing the recommended dose noted in the package insert and previous human reports ,18. The When all study protocols were completed, the thermodilution catheter and sheath introducer were removed, and manual astriction was performed at the catheterization sites. All dogs were recovered from anesthesia. Subsequently, amoxicillin  and robenacoxib  were administered. After completing the study protocol, all the dogs were transferred to another study at our institution.Right heart catheterization was performed by a single investigator (YY) using a thermodilution catheter . All hemodynamic data were randomly analyzed under the direction of another investigator using hemodynamic analysis software . Lead II electrocardiogram was simultaneously recorded. Using the thermodilution technique, a 3-mL ice-cold saline solution was rapidly injected from the proximal port three times to measure RV cardiac output and stroke volume .max and RV dP/dtmin, respectively). Additionally, the right atrial pressure and central venous pressure were measured at the beginning and end of the study protocol. RV SV was obtained by dividing the RV CO by the heart rate calculated from the R-R interval at the time of RV CO measurements. RV CO and SV were normalized by body surface area, and the mean values from three measurements were used for statistical analysis.All hemodynamic variables, except for RV CO and SV, were obtained from 10 consecutive sinus rhythms at the end-expiratory phase, and the mean values were used for statistical analysis. In this study, the following indices were measured as the RV hemodynamical variables: pulmonary artery wedge pressure (PAWP), PAP , RV pressure  and the maximal and minimal first derivative of RVP  and a 3.5–6.9 MHz transducer. Lead II electrocardiography was simultaneously performed, and data were displayed on the images. All data were obtained from at least five consecutive cardiac cycles in sinus rhythm during the end-expiratory phase. All echocardiographic data were randomly analyzed by the same investigator who performed right heart catheterization and by a well-trained cardiologist (YY) under the direction of another investigator using an offline workstation . This study used the mean values from three consecutive cardiac cycles for statistical analyses.The following variables were obtained to evaluate the left ventricular (LV) morphology and function: LV volume, ejection fraction and LV SV and CO. The end-diastolic and end-systolic LV volume was measured using the biplane modified Simpson’s method and the left apical two- and four-chamber view and was normalized by body surface area  ,21. LV SIn this study, end-diastolic and end-systolic RV areas , RV fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE) were measured using the left apical four-chamber view optimized for the right heart (RV focus view) ,24. The Furthermore, in this study, we calculated systemic vascular resistance (SVR) and PVR using hemodynamic and echocardiographic variables.The mean systemic arterial pressure was obtained using the oscillometric method, and the mean value of three measurements was used for statistical analyses .In this study, two-dimensional speckle tracking echocardiography (2D-STE) was performed as a precise indicator of LV and RV function. As the LV functional variables, LV longitudinal and circumferential strain  were measured using the left apical four-chamber view and the right parasternal short-axis view at the level of papillary muscle, respectively . The RV https://www.jichi.ac.jp/saitama-sct/SaitamaHP.files/statmed.html; accessed on 9 December 2022) [All statistical analyses were performed using the EZR ver. 1.50 software (er 2022) . Continut test  or Friedman rank sum test with subsequent pairwise comparisons using the Bonferroni-adjusted Wilcoxon signed-rank sum test . Additionally, the effects of pimobendan on hemodynamic and echocardiographic variables were evaluated using a paired t test  or Wilcoxon signed-rank sum test . Furthermore, one-way analysis of variance with subsequent pairwise comparisons using the Bonferroni-adjusted Student’s t test  or Kruskal-Wallis test with subsequent pairwise comparisons using the Bonferroni-adjusted Mann-Whitney U test  was performed to compare systolic PAP and PVR after administration of the examined drug at the maximal dose. Statistical significance was set at p < 0.05 for all statistical analyses.The normality of the data was evaluated using the Shapiro–Wilk test. The effects of each drug  on hemodynamic and echocardiographic variables were evaluated using a repeated-measures analysis of variance with subsequent pairwise comparisons using the Bonferroni-adjusted paired All right heart catheterization- and echocardiography-derived variables were obtained at all time points. The right atrial pressure and central venous pressure at the beginning of the study protocol were 3.4 ± 0.9 mmHg and 3.2 ± 0.9 mmHg, respectively, and those at the end of the study protocol were 3.7 ± 0.9 mmHg and 3.2 ± 0.8 mmHg, respectively.max, RV CO and RV SV compared with baseline and 2–5 ng/kg/min epoprostenol. SVR decreased significantly after administering epoprostenol at 15 and 20 ng/kg/min.The results of hemodynamic and echocardiographic variables are summarized in p = 0.048; 20 ng/kg/min: p = 0.048 and 0.04, respectively).No significant changes were observed in the LV and RV morphological indicators (LV volume and RV area) for echocardiographic variables. However, LV functional indicators, such as ejection fraction, LV SV, LV CO and 2D-STE-derived LV-SL and LV-SC, were significantly increased, especially after epoprostenol administration at 20 ng/kg/min. The RV-SL also increased with 15 and 20 ng/kg/min epoprostenol compared to baseline and 2 ng/kg/min epoprostenol . Additionally, 5 µg/kg/min dobutamine increased PVR compared to baseline (p = 0.02), whereas 10 µg/kg/min dobutamine showed no significant difference from baseline (p = 0.98). RV CO significantly increased with 10 µg/kg/min dobutamine, and RV SV also increased with 5 and 10 µg/kg/min dobutamine administration. The 5 and 10 µg/kg/min dobutamine significantly increased systolic SAP compared to the baseline . No significant difference was observed in SVR with dopamine administration.p < 0.01), and LV CO was significantly increased with 10 µg/kg/min dobutamine compared to baseline (p = 0.04). RV functional indicators, such as RV FACn, TAPSEn and RV-SL, also increased with dobutamine administration in a dose-dependent manner.For echocardiographic variables, LVESVI was significantly decreased, and ejection fraction, LV SL, and LV-SC increased significantly with dobutamine administration in a dose-dependent manner. LV SV increased significantly with 5 and 10 µg/kg/min dobutamine compared to baseline . Systolic and diastolic RVP and RV SV increased significantly with 3 and 5 µg/kg/min dopamine compared to baseline . The RV dP/dtmax increased significantly with 3 and 5 µg/kg/min dopamine compared to baseline (both p = 0.048), and the RV dP/dtmin decreased significantly with 5 µg/kg/min dopamine compared to baseline (p = 0.049). The 5 µg/kg/min dopamine significantly increased systolic SAP and SVR compared with baseline .p = 0.045). Additionally, 2D-STE-derived LV-SL and LV-SC increased significantly following dopamine administration in a dose-dependent manner. RV functional indicators, including RV FACn, TAPSEn and RV-SL, increased significantly with dopamine administration in a dose-dependent manner.Although no significant change was observed in LV volume for echocardiographic variables, ejection fraction was significantly increased with 3 and 5 µg/kg/min dopamine compared to baseline . In contrast, systolic PAP and PVR after 20 ng/kg/min epoprostenol administration were significantly lower than those after administration of 10 µg/kg/min dobutamine and 5 µg/kg/min dopamine . Additionally, a significant difference was observed in systolic PAP after 10 µg/kg/min dobutamine and pimobendan administration (p = 0.03).This study investigated the efficacy of epoprostenol, comparing it with various cardiac drugs for acute heart failure in a canine model of chronic PH. In this study, 15 to 20 ng/kg/min epoprostenol significantly decreased PVR and improved LV and RV function and pulmonary and systemic circulation without increasing PAP and RVP. These results suggested that epoprostenol might affect canine PH as well as human PH. Additionally, our pimobendan results supported the efficacy of pimobendan in canine PH, in line with a previous report. In contrast, although catecholamines (dobutamine and dopamine) significantly increased pulmonary and systemic circulation, the drugs also increased PAP and RVP. Our results indicate caution when using catecholamines in dogs with PH.To the best of our knowledge, this is the first study to evaluate the effect of epoprostenol on left and right heart hemodynamics in canine models of chronic PH. Although 2 to 10 ng/kg epoprostenol showed no significant changes in hemodynamic and echocardiographic indices, higher doses (15 to 20 ng/kg/min) of epoprostenol showed significant positive effects, especially in PVR, SVR, LV and RV function, and cardiac output from the LV and RV without worsening of PAP through pulmonary and systemic vasodilating effects. These results support the clinical utility of epoprostenol in canine PH. However, the doses observed in this study were higher than those recommended for human PH . The resRegarding catecholamines, the inotropic effects of dobutamine and dopamine significantly increased LV and RV function and CO in a dose-dependent manner. These results indicate that catecholamine might be effective against cardiac dysfunction and circulatory insufficiency associated with PH. However, PAP and RVP also increased with catecholamine administration. These results suggest that catecholamines might not fundamentally improve PH pathophysiology and rather worsen RV loading conditions, which is in accordance with a previous report in human medicine . TherefoIn this study, pimobendan administration significantly increased LV and RV cardiac function and CO without worsening PAP or epoprostenol levels. The results of PAP, PVR, LV and RV functional variables were consistent with those of a previous report of canine models of chronic embolic PH . AlthougThis study had several limitations. First, this study used canine models of chronic PH without symptoms of right heart failure . The results might have changed in the clinical cases and those with more progressed PH. Second, this study could not monitor right atrial pressure and central venous pressure throughout the study protocol. Therefore, SVR cannot be measured accurately. Additionally, rapid infusion of iced saline solution was performed many times in this study, which might have caused differences in volume loading conditions when examining each drug. However, these pressures were not abnormally high and did not change between the beginning and the end of the study protocol. Therefore, the influence of the right atrial pressure and central venous pressure was considered minimal. Third, this study investigated and compared the effects of various drugs on hemodynamics and cardiac function in the same order. Although a washout period was established between each drug to ensure that hemodynamic and echocardiographic variables had returned to the same level as at the beginning of the study protocol, the influence of the drugs already administered might not be ruled out completely. Furthermore, because this study did not establish placebo control, the potential impact of this study protocol was unclear. Finally, we could not perform an a power calculation in this study, and the small sample size might have decreased the statistical power.In conclusion, this study revealed that high-dose epoprostenol significantly decreased PVR and SVR and increased LV and RV cardiac function as well as CO in canine models of chronic PH. Although a significant decrease in PAP was not observed, epoprostenol could help effectively treat PH and associated right heart failure in dogs. In contrast, dobutamine and dopamine, empirically used to treat PH, significantly increased PAP, RVP, and LV and RV function. Although catecholamines would be effective in cardiac dysfunction attributable to PH, our results suggest that they might worsen PH pathophysiology, which encourages careful monitoring when using catecholamines for treating PH. Pimobendan, as well as epoprostenol, improved LV and RV function and CO without increasing PAP. However, improvements in PH pathophysiology through the vasodilating effect of pimobendan might be milder than that of epoprostenol. Further studies are needed to investigate the actual clinical cases of PH due to various causes and the efficacy of combination therapy with epoprostenol and inotropic drugs.


Background: Right ventricular (RV) involvement in Anderson–Fabry disease (AFD) is well known in the advanced stages of the disease RV hypertrophies, but little is known about the early involvement. The aim of our study was to assess RV function in AFD patients at diagnosis. Methods: A total of 23 AFD patients and 15 controls comparable for age and sex were recruited. A complete 2D standard echo with 3D volumetric and strain analysis of RV was performed. Results: Two patient populations, comparable for clinical baseline characteristics were considered. RV free wall thickness was significantly increased in the AFD group. No significant differences in standard RV indices  were found. A 3D volumetric analysis showed reduced RV ejection fraction and lower values of longitudinal septal, free wall and global longitudinal strain (GLS) in AFD patients. RV free wall thickness significantly correlated with both free wall RV LS and RV GLS. In multiple linear regression analysis, RV free wall thickness was independently associated with RV GLS even after correction for age and heart rate. Conclusions: In AFD patients, 3D echocardiography allows for the identification of early subclinical functional impairment of RV. RV dysfunction is independently associated with RV hypertrophy. Anderson–Fabry disease (AFD) is a lysosomal storage disorder also known as diffuse angiokeratoma or α-galactosidase A  deficiency. The clinical manifestations are caused by a mutational hit in the GLA gene, located on the X chromosome and encoding for the lysosomal enzyme α-galactosidase A . The mutation causes a progressive intracellular accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids, causing tissue accumulation and multi-organ damage affecting cardiovascular, renal, gastrointestinal, cerebrovascular, neurological, auditory, ocular and skin systems . The patAFD cardiomyopathy can mimic the clinical and structural features of hypertrophic cardiomyopathy (HCM) . LVH is Accurate medical history and complete physical examination should be obtained at the time of diagnosis. The suspicion of AFD has to be raised in patients with LVH in the presence of the following typical signs and symptoms: corneal opacity, angiokeratoma, hypohidrosis, albuminuria and acroparesthesia. Even so, in some rare cases, there could only be cardiac involvement; thus, the diagnosis of AFD is challenging even with advanced imaging techniques. In the last two decades, enzyme replacement therapy (ERT) or chaperone therapy with Migalastat has been demonstrated to be effective in reducing the accumulation of glycosphingolipids in the different tissues, including cardiac myocytes. ERT should be started in the subclinical disease stages before the development of irreversible target organ damage. Accordingly, early diagnosis and treatment of cardiac involvement in patients and affected family members is a crucial aspect of AFD management ,12,13,14Standard echocardiography is the first-line imaging for the identification of the typical features of AFD cardiomyopathy, both structural and functional changes such as unexplained left ventricular hypertrophy with RV free wall thickening, preserved left ventricular ejection fraction (LVEF) until end-stage of the disease and progressive diastolic dysfunction ,16. HoweCardiac involvement in AFD patients is characterized by LV geometry changes starting with concentric remodeling commonly progressing to concentric hypertrophy . A peculbinary sign  was considered the pathognomonic hallmark to distinguish AFD patients from those with familial HCM [In the past, the lial HCM . Despitelial HCM ,23.Regarding LV diastolic function, it is compromised early in patients with AFD. In a report published by Palecek et al., 44% of 81 echocardiographic examinations in 35 patients with AFD had a normal LV filling pattern, while 56% showed an impaired LV diastolic function. Of these, only 4% had a restrictive filling pattern, while 60% had a pseudo-normal filling pattern, and 36% impaired relaxation . The diaIn the setting of preserved LVEF, AFD cardiac involvement reveals an association between diastolic dysfunction indices, namely E/e’ ratio and the presence of late gadolinium enhancement (LGE), an important index of myocardial fibrosis recognized by cardiac magnetic resonance (CMR) imaging. In fact, a cut-off of 14.8 for the septal E/e’ ratio has been demonstrated to be the best predictor of the presence of LGE .Impairment of diastolic function leads to the dilatation of the left atrium. Left atrial dilatation and reduced atrial compliance occurs in the early stages of AFD, even before LVH ,32,33, mAbnormal glycosphingolipids accumulation may commonly also involve the valvular structures . Aortic Right ventricular hypertrophy (RVH)  is commoCurrent studies in the literature report discordant data on the systolic function of the right ventricle in patients with AFD. Kampmann et al. found that severe RV hypertrophy in Fabry disease is accompanied by severely depressed systolic function as indicated by a depressed tricuspid annulus movement and increased ratio PEP (pulmonary pre-ejection period)/ET (pulmonary ejection time) . The finRegarding the RV diastolic function of patients with AFD, data currently present in the literature agree with the finding of diastolic dysfunction in about half of the cases ,40,41.Conventional echo parameters such as fractional area change, tricuspid annular plane excursion and tissue Doppler S’ are recommended measures to assess RV systolic function. However, they have major limitations of being angle-dependent, load-dependent and not fully representing RV global function . Three-dSpeckle tracking analysis in routine echocardiography has deeply increased diagnostic performances by recognizing intrinsic myocardial dysfunction before LVEF reduction in a subclinical stage . In a reWhen comparing HCM and AFD entities, the longitudinal strain pattern is notably different between affected patients. Hypertrophic cardiomyopathy presents a reduction of LS in the septum, while in AFD patients at late-stage, lateral and posterior walls are the most affected ones .The diagnostic work-up of Fabry disease is completed by cardiac magnetic resonance (CMR) which accurately provides differential diagnoses of LV hypertrophy. Late gadolinium enhancement (LGE) can be found in the late stages of the disease. Interestingly, echocardiographic parameters such as the reduction of inferolateral region strain have been shown to predict the presence of LGE on CMR . This alRecent anatomopathological findings demonstrated that structural changes such as the accumulation of globotriaosylceramide affect all cardiac cell types, including myocardial cells of the right ventricle (RV) and left atrium (LA) .There is evidence in a study performing comprehensive myocardial analyses with 2D-STE and cardiac MRI in AFD patients and a large cohort of healthy subjects that patients with Fabry had significantly lower functional myocardial values of RV and LA, even when conventional cardiac parameters were normal . In addiGLA) gene test was performed using the dried blood filter paper test. In male patients, diagnosis was made by demonstration of a deficient activity of alfa-galactosidase in plasma; female patients were directly tested for possible mutations in the GLA gene, and then evaluated for α-GalA activity when positive at the genetic test.For the purposes of the study, 23 subjects with AFD classical variant were recruited at diagnosis  and a group of 15 healthy controls, comparable for age (38 ± 12 years) and sex (M/F = 10/5). All participants gave written informed consent to the procedures before entering the study. The study was approved by the local Ethical Committee (protocol number 1233/19). We excluded patients with relevant cardiac signs/symptoms, patients affected by cardiac risk factors , patients already under enzyme replacement therapy and patients with poor echocardiographic imaging. All patients had confirmed diagnosis of AFD: for all subjects, the evaluation of α-GalA activity and the galactosidase alpha  equipped with a 2.5 MHz phased-array transducer according to the American Society of Echocardiography (ASE)/European Association of Cardiovascular Imaging (EACVI) standardization . Blood pA comprehensive assessment of RV geometry, systolic and diastolic function  was perfA complete 3D analysis  of the rThe focused RV apical four-chambers view was used for the assessment of peak systolic RV global longitudinal strain (RV GLS), longitudinal peak systolic strain of the RV free wall  and longitudinal strain of interventricular septum  . For STEt-test. Univariate correlates of a given variable were evaluated by least squares linear regression. The null hypothesis was rejected at 2-tailed p < 0.05.Statistical analysis was performed by SPSS package, release 12 . Continuous variables are presented as mean ± SD. Categorical variables are presented as absolute numbers and percentages. Differences in continuous variables between the whole Fabry population vs. controls were analyzed using Student’s As can be seen from the collection of data in As can be seen from data in p < 0.0001).The data showing the greater discrepancy between the two groups of subjects is certainly the thickness of the free wall of the RV, which significantly increased in the AFD group compared to the 2D echo controls  and RV ESV (p < 0.0001) with a likely reduced RV EF (p = 0.009) in the subjects diseased, as well as the longitudinal septal strain , free wall strain  and the global longitudinal strain (RV GLS) .As can be seen from the data in p = 0.05) and RV GLS .As can be seen from data in p = 0.004) .In the multiple linear regression analysis shown in The results of our study clearly show that there is early involvement of the right ventricle in patients with AFD and that the latter can be detected using advanced echocardiographic techniques. In fact, the presence of conflicting data in the literature on the systolic function of the right ventricle in patients with AFD is due to the type of analysis performed: evaluations were carried out using standard echocardiographic parameters such as TAPSE, FAC and RVS. This is the first study that evaluated the right ventricle and its function in AFD patients using 3D echocardiography. This made it possible to overcome the limit linked to the complexity of the geometry of the right ventricle, obtaining a reliable estimate of the end-diastolic, end-systolic volumes and the ejection fraction of the right ventricle. Indeed, several studies have shown that right volumetric evaluation by 3D echocardiography correlates well with the volumes derived from CMR in different groups of patients ,58,59. TWith regard to strain, several studies have evaluated RV strain ,60,61: tIn our study, a univariate analysis was also performed which evaluated the correlation between the RV free wall thickness and both free wall RV LS and RV GLS; multiple linear regression analysis showed that the thickness of the free wall of the RV was independently associated with the RV GLS even after correction for age and heart rate. This result is extremely important as it underlines how an accurate echocardiographic evaluation using 3D-STE can allow us to highlight, in an early manner, strain alterations that correspond to the degree of hypertrophy of the ventricular walls which, if recognized early, provide the possibility of early treatment.Our study allows us, therefore, to conclude that in patients with AFD, 3D echocardiography allows us to identify an early subclinical functional damage, not otherwise detectable by standard ultrasound Doppler.The strain, and in particular GLS, is able to provide additional information and is therefore crucial to the basic echocardiographic examination, highlighting in an early manner the systolic changes present in conditions, such as hypertrophic cardiomyopathy typical of AFD, and susceptible to a progression, even important and sudden, which obviously wants to be averted with appropriate and timely therapy.And it is precisely the prospect of an early administration of cardioprotective drugs that is the final objective of this study. In fact, if it is true that it is possible to identify in an early manner a significant reduction of GLS in AFD patients and, therefore, a myocardial compromise indicating the development of imminent cardiomyopathy, it is also true that with the acquisition of such data, it is possible to obtain the appropriate indication to the administration of therapeutic treatment, which prevents the progression of myocardial compromise and safeguards these patients from fatal myocardial damage, typical of the frequent death in AFD.


Despite the long-standing neglect, there is now a mounting interest in the left atrium (LA) physiology.Nowadays, it is widely acknowledged that LA coordinates the left ventricular (LV) filling and the cardiovascular systo-diastolic functions through its roles as a reservoir, conduit, and booster pump. During ventricular systole, it serves as a reservoir for pulmonary venous return, while in early ventricular diastole, it acts as a conduit for pulmonary venous return. During late ventricular diastole, it also functions as a booster pump, enhancing ventricular filling.The interdependent nature of the LA functions serves as a compensatory mechanism, aiding in the facilitation of LV filling in individuals with myocardial disease. Moreover, the atrial reservoir phase plays a crucial role in LV filling as it accumulates energy during the ventricular systole, which is subsequently discharged upon the opening of the mitral valve.Notwithstanding the availability of a wide range of echocardiographic and Doppler techniques for measuring LA function, the preferred method is typically the speckle-tracking echocardiography (STE) strain analysis, which captures both the global and regional deformation of the myocardium by tracking the natural acoustic markers (speckles) produced through the interaction between ultrasound waves and the myocardial tissue on a frame-by-frame basis.Understanding the LA deformation plays a critical role in congenital heart disease and cardiomyopathies  where there is an unmet need to anticipate left myocardial failure on a subclinical basis.The employment of left atrial (LA) strain is still poorly understood in children, although it is known to be helpful for the assessment of diastolic function in adults. For this purpose, Sabatino et al.  investigNew insights derived from LA strain assessment in congenital heart diseases have been set up by Nemes et al.  in theirAn interesting use of the LA strain was implemented by Esposito et al. , which aCurrently, atrial speckle tracking echocardiography strain has been poorly studied in the pediatric population undergoing cardiac surgery. For this purpose, Cantinotti et al.  presenteWe have observed that studies on the echocardiographic evaluation of strain in pediatric age are progressively increasing; however, this is not the only method that can be used to evaluate atrial deformation. Stojanovska et al.  investigWhen compared to the LV, strain imaging of the left atrium (LA) is considered more challenging and time-consuming among most cardiologists and echocardiographers. This is primarily due to several factors, including the far-field location and the thin walls of the atrium, the presence of the appendage and the pulmonary veins, and the requirement for obtaining non-foreshortened views of the atrium.Nevertheless, there are compelling reasons to utilize LA strain in the clinical setting. Firstly, LA strain combines multiple parameters into a single reliable and reproducible measurement. Secondly, LA strain has demonstrated significant diagnostic value and an ability to predict cardiovascular events, particularly in patients with cardiomyopathies and congenital heart disease, although its applicability is not limited to these conditions.Considering the extensive research conducted on this parameter, it is now imperative to integrate it into diagnostic stratification strategies and consensus documents.


Inducing recovery in myocardial ischemia is limited to a timely reopening of infarct vessels and clearing the cardiac microcirculation, but additional molecular factors may impact recovery.In this scoping review, we identify the paradigm shifts decoding the branching points of experimental and clinical evidence of pressure-controlled intermittent coronary sinus occlusion (PICSO), focusing on myocardial salvage and molecular implications on infarct healing and repair.The reporting of evidence was structured chronologically, describing the evolution of the concept from mainstream research to core findings dictating a paradigm change. All data reported in this scoping review are based on published data, but new evaluations are also included.Previous findings relate hemodynamic PICSO effects clearing reperfused microcirculation to myocardial salvage. The activation of venous endothelium opened a new avenue for understanding PICSO. A flow-sensitive signaling molecule, miR-145-5p, showed a five-fold increase in porcine myocardium subjected to PICSO.r2 = 0.90, p < 0.05; r2 = 0.98, p < 0.03), suggesting a flow- and pressure-dependent secretion of signaling molecules into the coronary circulation. Furthermore, cardiomyocyte proliferation by miR-19b and the protective role of miR-101 against remodeling show another potential interaction of PICSO in myocardial healing.Verifying our theory of “embryonic recall,” an upregulation of miR-19b and miR-101 significantly correlates to the time of pressure increase in cardiac veins during PICSO (Molecular signaling during PICSO may contribute to retroperfusion toward deprived myocardium and clearing the reperfused cardiac microcirculation. A burst of specific miRNA reiterating embryonic molecular pathways may play a role in targeting myocardial jeopardy and will be an essential therapeutic contribution in limiting infarcts in recovering patients.  Nothing conserves ischemic myocardium better than early reperfusion. However, an uncontrolled inflow of oxygenated blood into the damaged microcirculation has many side effects, a phenomenon known to cardiac surgeons since the pre-cardioplegia era in open-heart surgery –3.One option for myocardial protection evolved from an old idea when Pratt used cardiac veins to access the myocardium in isolated feline hearts . This co”  . After a” .clinicaltrials.gov; five are completed, one is terminated, one is not yet recruiting, and recently two, among one the randomized trial, are recruiting. The objective of the randomized trials is “to assess the efficacy and safety of Pressure-controlled intermittent Coronary Sinus Occlusion (PICSO) therapy started post flow restoration but before stenting during the percutaneous coronary intervention (PCI) compared to standard PCI in the setting of acute ST-segment elevation anterior myocardial infarction (STEMI)” .It took exactly 30 years after this publication until another randomized trial started, recruiting patients with acute coronary syndromes investigating PICSO in a prospective, multicenter, randomized, controlled study during reperfusion aiming to reduce infarct size. Currently, 10 PICSO trials are listed on Current clinical trials of PICSO in early reperfusion mimic the study objective of our first trial in open-heart surgery and represent the mainstream of PICSO research., as verified by Kenner in 1985, using blood density measurements during controlled sequences of coronary sinus occlusions, was the first indication of a branching point. The underappreciated complexity of Kenner's microhematocrit measurements in cardiac veins is now, in retrospect, the critical, still valid crossroad of PICSO research. Although corroborated by several authors using different methodologies of coronary venous retroperfusion and measurement modalities, like contrast disappearance or xenon washout, the impact and consequence of this scientific achievement, not well understood, remained unscrutinized , formulated “the dose makes the poison,” which is also relevant in myocardial drainage limitation. Gradual and timed outflow resistance may be beneficial in ameliorating ischemia. However, sudden and complete occlusion of outflow of cardiac veins is detrimental and must be avoided. The experimental and later clinical evidence shows that PICSO induces salvage by redistributing flow into the deprived myocardium . Recently, Egred et al. reported in patients with ACS treated with PICSO a significant absolute of 6.9%, a 33% relative decrease of infarct size as a percentage of left ventricular mass in a propensity-matched analysis compared to historical controls (INFUSE MI) measured by CMR 5 days after the infarct  region as well as in the right ventricle (RV) with independent myocardial drainage.p < 0.05). Although miR-21 has repeatedly been associated with cardiac events such as response to oxidative stress, NF-kB activation, or fibrosis formation, its expression was chosen as an averagely expressed miRNA, which was subject to minor variation in our analyzed cardiac tissue samples, consistent with our theory, that PICSO alone does not change miR-21 expression  .Since the posterior interventricular vein flow is typically unhindered by PICSO, we consider that activating collaterals and molecular events or soluble factors released and washed into the independent drainage zones are causing positive effects on vasodilation, as first described by Weigel et al. in 2007 .In 2018, we reported acute molecular changes in secreted molecules by PICSO. Eight out of 32 patients undergoing resynchronization device implantation were treated with PICSO for 20 min. Coronary sinus blood samples were collected before and after PICSO or 20 min in untreated patients, and pre-interventional sera were compared to post-interventional sera in both groups as well as among groups. The miRNA patterns between samples collected before and after the treatment and compared to controls were differentially expressed. In addition, these samples were used as a medium for cultures with cardiomyocytes from cardiac tissue harvested during heart transplantation, also displaying differences in proliferation . Comparep < 0.048) and miR-145 (p < 0.047) increased, both targeting a network of transcription factors, including KLF-4 (Krüppel-like factor 4), an evolutionarily conserved member of the KLF family of zinc finger transcription factors promoting differentiation and repress proliferation of vascular smooth muscle cells. In addition, other transcription factors showed favorable trends by PICSO, as MeF2a (myocyte enhancer factor 2a), a prominent member of the transcription family, acting as a myocardial enhancer in cardiac development and adaption to hypertension-induced cardiac hypertrophy, although not statistically significant, due to the small number of patient tested , alleviating endothelial cell apoptosis. The miR-17-92 cluster is a highly conserved gene cluster that encodes various conserved miRNAs, including miR-19b (p < 0.001) and adult cardiomyocytes (p < 0.004) harvested from a transplant recipient compared with controls. In addition, adult cardiomyocytes showed a seven-fold increase of the transcription factor KLF-4 protein when cultured with treated sera compared with controls. Increased miR-19b and the observed proliferation induced by PICSO suggest a causal relationship , suggesting a flow- and pressure-dependent secretion of signaling molecules into the coronary circulation. Our observed relationship in patients with heart failure corroborates Weigel's correlation between heme oxygenase with the developed pressure in coronary veins during PICSO, indicating cytoprotection during ischemia/reperfusion injury. For the first time, this causal relationship connects the hemodynamic consequences of PICSO via signaling events to published evidence on the proliferation of cardiac cells -induced injury by targeting DNA damage-inducible factor 4 (DDIT4) to regulate autophagy, indicating that miR-101 or DDIT4 may be potential therapeutic targets for heart injury and may play a role in apoptosis .Interestingly, miR-101 plays a protective role against cardiac remodeling following MI via inactivation of the RUNX1 (runt-related transcription factor1), proposing miR-101 and RUNX1 as potential therapeutic targets for MI , 65.Recently, Wang et al. showed that miR-101a-loaded mesenchymal stem cells in extracellular nanovesicles significantly improved heart function, decreased infarct size, and decreased fibrosis after MI even when injected into the myocardium 13 days after the infarct, suggesting the equivalent upregulation of miR-101 in PICSO patients as a favorable event .p < 0.023). Both miR-320b miR-25 (p < 0.023) decreased, and proposed targets of anti-miR application to improve contractility in the failing heart. Wang 2014 provided a novel mechanism for the exosomal miR-320 functionally downregulated its target genes IGF-1, Hsp20, and Ets2  (Other disadvantageous non-coding RNA found in our study on acute changes in patients with heart failure influenced by PICSO are miR-320b and miR-25 (yocytes) . In the yocytes) .Therefore, since signaling molecules sequestered into the coronary venous blood are differentially expressed by PICSO, and relate to pressure increase during PICSO, their role in ACS outcome can be predicted. Relating PICSO parameters to PICSO effects on non-coding RNA coincide with the report by Syeda et al., convincingly showing that the sequence of occlusion release phases and the increase in systolic pressure over time is related to the amount of myocardium salvaged . AlthougAlso, the contribution by Weigel et al. was found in a positive and statistically significant correlation between mean and developed peak coronary sinus pressure and the HO-1 and VEGF gene transcription. These findings are now completed with a relationship between signaling molecules and PICSO parameters, strongly suggesting that mechanical strain and stretch produced by the pulsatile action of the reflowing blood in the deprived venous vasculature triggers the activation of a genomic program within the myocardium .Clearing ischemic/reperfused microcirculation and its relationship to myocardial salvage is the mainstream PICSO claim to be tested in ongoing clinical trials. PICSO can influence the pathophysiology of structural changes in the post-reperfusion myocardium. The plasma skimming theorem of PICSO was tested using microhematocrit changes in cardiac veins substantiating measurements of blood density as the crucial parameter of PICSO effectiveness. Separating cellular components in more prominent veins and pressing plasma into the microcirculation, thus varying hematocrit levels measured in the coronary sinus, is the typical denominator improving conductance in the reperfused microcirculation. This effect seems to be the principal cause of impact on molecular secretion see . A more p < 0.044)  .p < 0.0149). Adjusting for restenosis, the risk for MACE was nine times higher for the control group than for the PICSO group , as an index for injured microcirculation, was also associated with a higher incidence of MACE in patients with acute coronary syndromes . FurtherThe second important mechanism, interpreting our results on restenosis and MACE, is the molecular signaling event, influencing the relationship between intrinsic apoptosis, necroptosis, and pyroptosis, influencing infarct healing and correcting the inflammatory process in ACS. In our study, the recurrence of reinfarction was reduced. The relative risk for re-MI was 17 times higher for the control group than for the PICSO group, even after including other risk factors .In a recent article, Crea summarized the importance of inflammation in post-ischemic events, implying the inflammatory risk and its relationship to the recurrence of ischemic events .As said, PICSO seems to activate alternate pathways limiting inflammation and reopening canonical pathways described in our “Embryonic Recall” hypothesis. In addition, the plasma skimming machinery of PICSO next to producing molecular signals reopens the venous microcirculation, liberating edema and toxic metabolites.Molecular events during reperfusion of a deprived myocardial territory are a complex problem with multiple signaling and sometimes counteracting events. Therefore, it can be expected that a burst of several non-coding RNA, many hitherto unknown, in context with other regenerative molecules, are involved in the signaling event, both induced by the disease process and by PICSO .Reversal of adverse remodeling to prevent heart failure is one of the targets of recent research, and measurements of ventricular volumes are a diagnostic option , 75. In We are expecting results of ongoing clinical trials of PICSO research since they will eventually answer the questions asked 30 years ago and whether it is safely applicable in the routine logistics of cath labs in the 2020s, correcting reperfusion injury. It remains to be seen whether infarct size reduction is the correct signal, relating patient outcome with apparent advantages for patient survival and quality of life.These hypothesis-generating observations of a noticeable paradigm change will guide the exploration of the novel approach to treating myocardial microcirculation during jeopardy. In addition to salvage, an overall cardioprotective effect can be anticipated, leveraging problematic infarct size measurements as expected in our hypothesis. Hemodynamic PICSO forces reopen the ischemic/reperfused microcirculation, mainly by redistribution of flow and washout, but initiating cascades of molecular signaling seems to be an essential factor as well. In the next step, corroborating molecular signs and signals of PICSO effects in pivotal trials is mandatory since we must verify heart failure studies of non-coding RNA in patients with acute myocardial infarction. More extensive, primarily clinical studies will eventually confirm molecular signaling as one of the significant effects and establish PICSO as valuable therapy for ischemic, reperfused microcirculation treatment in patients with STEMI and beyond.The future of clinical PICSO is based on an analytical appraisal of yesterday's conceptualization, an open eye for identifying cross roads, even unexpected counterintuitive findings, and an available vision of the future's scientific perspective in parallel to clinical evidence.This notion and the uncertainty of whether an additional infarct size reduction can be achieved as an add-on therapy during reperfusion dictates another paradigm change in PICSO research, concentrating on repair pathways and starting even before reperfusion. This newly defined PICSO target needs sophisticated technology and new clinical research perspectives to mitigate patient outcomes.The information presented here is a roadmap of findings with counterintuitive results forcing research into unexpected territories. What started as an anti-ischemic procedure developed into a complex signaling and network of molecular pathways. Abstracting scientific evidence warranted the formulation of our hypothesis, “embryonic recall.” It is apparent, however, that tested miRNAs are not the only signaling pathways, and many more molecular signals must be detected.The development of the PICSO concept bridged several decades and was started before revascularization therapies became routine. The current understanding of “time is muscle” and early revascularization nowadays limiting PICSO applications into the reperfusion period falls short, considering ambivalent results in determining reperfusion injury.Another significant limitation is that the administration of heparin interacts with miRNA activity as routine treatment in acute coronary syndromes and may be a serious disadvantage of a PICSO application.Therefore, future research must concentrate on the molecular role of PICSO in routine revascularization procedures. It may very well be that an application during ischemia on the way to the cath lab or at any other time during infarct healing supports recovery and may better interact with myocardial decay.


Echocardiography (ECHO) and cardiac magnetic resonance imaging (MRI) are used to observe changes in the left ventricular structure in patients with breast and gastric cancer after 6 cycles of chemotherapy. Based on the observed values, we aimed to evaluate the cardiotoxicity of anthracyclines in cancer patients and to analyze the consistency of the two examination methods in assessing left ventricular function after chemotherapy.From January 2020 to January 2022, the data of 80 patients with malignant tumors who received anthracycline chemotherapy  and 40 healthy volunteers (Control group) were retrospectively collected. Serum high-sensitivity cardiac troponin T (hs-cTnT) levels were detected by an automatic immunoassay analyzer. Left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) were measured by cardiac MRI and 2-dimensional ECHO using the biplane Simpson’s method.P < 0.05). In addition, LVEDV, LVESV and LVEF measured with MRI were higher than those detected by ECHO in cancer patients after 6 cycles of chemotherapy (P < 0.05). And the Bland-Altman plot analysis showed that LVEDV, LVESV and LVEF measured by the two examination methods were in good agreement.Compared with baseline values, serum high-sensitivity cardiac troponin T (hs-cTnT) levels were significantly increased in patients with breast cancer and gastric cancer after 6 cycles of chemotherapy (Breast and gastric cancer patients exhibited elevated levels of hs-cTnT after 6 cycles of chemotherapy, indicating potential cardiotoxicity. Additionally, cardiac MRI and 2-dimensional ECHO showed good agreement in assessing left ventricular function, with ECHO tending to underestimate volume measurements compared to MRI. Before chemotherapy, there was no significant difference among them in age, body mass index, systolic blood pressure, diastolic blood pressure, heart rate, history of hypertension, history of cardiovascular disease, tumor stage, serum hs-cTnT, LVESV, LVEDV and LVEF (P < 0.001) (Table P < 0.001) (Table Serum hs-cTnT level in patients with gastric cancer after chemotherapy [9.3 3.4–882.1) pg/mL] was increased compared with that before chemotherapy [8 (2–14) pg/mL], and the difference was statistically significant (.1 pg/mL]P < 0.05)  Table . And the5) Table .Although ANT represents a class of highly effective and broad-spectrum anticancer drugs that help improve patient survival and reduce tumor recurrence, they are also cardiotoxic and may impair myocardial function. Therefore, early and accurate assessment of cardiac function status has important clinical significance for patients receiving ANT chemotherapy . Blaes eCurrently, the techniques for assessing left ventricular function after chemotherapy in cancer patients include ECHO and cardiac MRI. ECHO is performed using color Doppler technology to evaluate heart function and heart structure, which can more carefully observe the size of the heart cavity, measure heart function, and observe the changes in the heart valve, including valve stenosis and valve insufficiency . MRI is Comparatively, we found that LVEDV, LVESV and LVEF measurements were lower in ECHO than in MRI, which was the same as Carly’s study . In addiOur study still has the following limitations. First, it was a single-center study with a relatively small sample size (including only 40 patients with breast cancer and 40 patients with gastric cancer), which might have affected the statistical power. Second, we only analyzed the left ventricular function in patients with breast and gastric cancer before and after 6 cycles of chemotherapy but lacked further validation compared with after other cycles of chemotherapy. Third, it should be noted that the cancer patients were included irrespective of their metastatic status and previous treatment (except for no previous treatment with ANT prior to this study), which might have affected the study results to a certain extent. However, in this preliminary study, all first-time ANT-treated patients were assessed to obtain a real-world representation of the general perspective of this regimen and agreement between MRI and ECHO. Also, sub-group analyses could not be performed for the different treatment stages due to the small number of cases assessed. Therefore, it is necessary to further expand the sample size and collect more data at different time points to strengthen the reliability of the experimental results.In conclusion, this study shows the potential cardiotoxic effects of anthracycline chemotherapy in breast and gastric cancer patients and highlights the importance of cardiac monitoring during treatment. Both ECHO and cardiac MRI can provide valuable information on cardiac function, with ECHO being more accessible, while MRI offers greater accuracy and comprehensive evaluation. The agreement between the two methods suggests that ECHO can be a useful tool for routine cardiac monitoring, while MRI may be more suitable for research or complex clinical situations. Further studies are needed to explore the long-term cardiac implications of anthracycline chemotherapy in cancer patients and validate our study findings.


Currently, the symptomatic status and left ventricular ejection fraction (LVEF) play a crucial role in aortic stenosis (AS) assessment. However, the symptoms are often subjective, and LVEF is not a sensitive marker of left ventricle (LV) decompensation. Over the past years, the cardiac structure and function research on AS has increased due to advanced imaging modalities and potential therapies. New imaging parameters emerged as predictors of disease progression in AS. LV global longitudinal strain has proved useful for risk stratification in asymptomatic severe AS patients with preserved LVEF. The assessment of myocardial fibrosis by cardiac magnetic resonance is the most studied application and offers prognostic information on AS. Moreover, the usage of biomarkers in AS as objective measures of LV decompensation has recently gained more interest. The present review focuses on the transition from compensatory LV hypertrophy (H) to LV dysfunction and the biomarkers associated with myocardial wall stress, fibrosis, and myocyte death. Moreover, we discuss the potential impact of non-invasive imaging parameters for optimizing the timing of aortic valve replacement and provide insight into novel biomarkers for possible prognostic use in AS. However, data from randomized clinical trials are necessary to define their utility in daily practice. The prevalence of valvular diseases is increasing with the prediction of by 2050 , especiaThis review focuses on the transition from compensatory LVH to LV dysfunction and heart failure in AS and the release of biomarkers associated with myocardial wall stress, fibrosis, and myocyte death. Moreover, we discuss the potential impact of non-invasive imaging parameters for optimizing the timing of aortic valve replacement (AVR) and provide insight into novel biomarkers for possible diagnostic and prognostic use in AS.Currently, the symptomatic status and left ventricular ejection fraction (EF) play a crucial role in the management of AS patients ,7. HowevThe progressive decrease in the area of the aortic valve determines a chronic pressure overload. The early adaptive manifestation of the ventricular myocardium is hypertrophy with LV diastolic dysfunction. Later, LV systolic dysfunction occurs, with myocardial contractile function and deformation becoming impaired. The left atrium (LA) also presents some morphological changes. The LA responds by increasing its volume to the chronic pressure overload, leading to a higher pulmonary venous and arterial pressure. The ventricular and atrial changes will result in heart failure, atrial fibrillation (AF), and symptom development. Thus, AS represents not only a valvular disease but a whole heart disease, often in patients with comorbidities. However, AS patients can be asymptomatic until the late stage of the disease.The presence of symptoms in severe AS patients was reported to be associated with smaller aortic valve area, higher degree of LVH, increased levels of plasmatic brain natriuretic peptide, but also with impaired LV diastolic function parameters, including increased LA dimensions ,10,11,12Since there is no other definitive treatment apart from AVR in AS, the time of intervention is crucial to optimizing the outcome for patients and their future quality of life. While for symptomatic severe AS patients, the AVR decision is clearly stipulated, the timing for intervention in asymptomatic severe AS patients is still subject to debate. Studies already reported that symptom development is associated with higher mortality, even after AVR. Asymptomatic patients with moderate-to-severe AS demonstrated unequivocal progression in the adverse cardiac remodeling within 12 months, with a significant increase in focal myocardial fibrosis (MF) . A multiOnce established, mid-wall late gadolinium enhancement (LGE) also accumulated rapidly, increasing by 75% each year on average, especially in patients with a high baseline fibrosis burden . This chLeft ventricular hypertrophy (LVH) develops early, in response to pressure overload from AS. The LV remodeling pattern may vary between patients depending on sex, age, and co-existent coronary artery disease (CAD) or hypertension . AlthougLVH and MF from chronically elevated LV systolic pressure result in diastolic LV dysfunction . The graThe term fibrosis is used in the literature to describe the excessive deposition of extracellular matrix (ECM) proteins in parenchymal tissues and typically reflects inappropriate or unrestrained activation of a reparative program . In AS, In the early stages of the disease, the process involves the myocardium diffusely, is interstitial, reactive to pressure overload, and potentially reversible .In the late stages of the disease, the fibrosis becomes substitutive and irreversible, with a focal distribution  due to tFrangogiannis identified the four mechanisms, which may induce the activation of the fibroblasts in heart failure associated with pressure overload . NeurohuThe gold standard for MF assessment is histological analysis obtained through endomyocardial biopsy, but non-invasive cardiac imaging may offer surrogate biomarkers .In AS, the increased pressure and wall stress are also present at the atrium level. The LA plays an important role in modulating LV filling and maintaining an optimal LV stroke volume, especially in patients with AS and LVH, through several different mechanisms. The LA acts as a reservoir during LV systole and isovolumic relaxation, filling with blood from the pulmonary veins; as a conduit during early LV diastole and diastasis, transferring blood into the LV via a small pressure gradient during early diastole and passively from the pulmonary veins during diastasis; as a booster pump during late LV diastole, contributing to LV stroke volume by 20–30% in normal subjects and significantly more when LV diastolic properties are impaired; and as a suction source, which refills itself in early systole . LV diasMF at the LA level is very important, leading to LA dysfunction with symptom occurrence and/or atrial fibrillation (AF). The remodeling process becomes irreversible if this LA fibrosis is extensive. Thus, early detection of LA dysfunction is mandatory for initiating specific therapeutic interventions .The increased LA pressure and wall stretch lead to the renin–angiotensin–aldosterone system (RAAS) and leukocyte activation—the main pathways to atrial fibrosis and cardiomyocyte hypertrophy .2+ overload and fibroblast proliferation [MMP, PAI-1, CTGF, and TGF-β [RAAS activation promotes the activation of hydrolysis phospholipase C (PLC), the activation of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, the release of reactive oxygen species (ROS), and it regulates the expression of profibrotic factors  . PLC actferation . The mitnd TGF-β . Smad 2/nd TGF-β . Ang II nd TGF-β . Sygitownd TGF-β . Ang II nd TGF-β . Thus, tnd TGF-β .Leukocyte activation is also triggered at the LA level with the subsequent release of inflammatory stimuli . Fibrobl2+-handling abnormalities, and autonomic neural dysregulation [Structural remodeling is one of the factors influencing the AF pathophysiology in AS, in addition to ion channel dysfunction, Cagulation . Fragão-gulation . The atrgulation . In AS, gulation . Researcgulation . Collagegulation .The assessment of LV remodeling and function is mandatory in all AS patients. Measuring the LVEF via the biplane method of discs is always recommended and, whenever feasible, via 3D echocardiography . HoweverIt is known that LV global longitudinal strain (GLS), assessed with speckle tracking echocardiography (STE), is an accurate and widely available marker of early, subclinical LV dysfunction, which occurs before LVEF impairment. The use of advanced echocardiography imaging allows the assessment of myocardial mechanics in terms of displacement, velocity, strain, and strain rate in longitudinal, radial, and circumferential directions. In AS, LV longitudinal strain is impaired, especially in the basal segments . The devThe parameters of LV systolic function, assessed via speckle tracking echocardiography (STE), were correlated with the presence of heart failure symptoms in AS. Moreover, GLS has proved useful for risk stratification in asymptomatic severe AS patients with preserved LVEF . StudiesEchocardiography also enables the assessment of atrial structural and functional changes. Progressive LA enlargement and impairment of all three components of LA longitudinal phasic function have already been demonstrated in patients with severe AS . LA sizeTwo-dimensional STE is recognized as a powerful, accurate imaging method for assessing the LA phasic function .Mateescu et al. proposed the LA systolic strain rate, in addition to AVA, as a tool for risk stratification in patients with asymptomatic AS . STE is Moreover, impaired LA longitudinal function predicted post-operative AF in patients who underwent AVR for isolated severe AS .However, O’Connor et al. reported that LA dilation does not reflect an intrinsic LA dysfunction, and alteration in LA strain parameters does not perfectly track the increase in LA size in severe AS patients . This fiPrevious data suggest that the presence of LA MF is independently associated with impairment of LA longitudinal function, with subsequent development of heart failure symptoms and/or AF . TherefoMoreover, experimental studies suggest that older age and chronic myocardial stretch may contribute to the development of both LA wall fibrosis and remodeling in severe AS, leading to intrinsic LA myocardial alterations and subsequent functional impairment .CMR has the advantage of combining anatomy and function multi-parameters with detailed soft tissue characterization. This is particularly important in AS, as understanding the myocardial damage and function may be clinically relevant, beyond the valve hemodynamics and obstruction. The use of CMR to detect MF is currently the most studied application of myocardial tissue characterization in AS patients . MF is tLate gadolinium enhancement (LGE) CMR is the gold standard imaging method for assessing focal, replacement fibrosis .The development of LGE in AS appears to be a marker of LV decompensation and predicts further rapid progression of fibrosis . ImportaT1 mapping techniques can provide overall assessments of the extracellular compartment, unlike LGE, which is insensitive to the detection of diffuse interstitial fibrosis. T1 mapping and extracellular volume fraction (ECV%) have prognostic significance across a range of cardiomyopathies. ECV% differentiates between intracellular and extracellular components of the myocardium. The indexed ECV has also been studied in AS, and this measure provides an estimate of the total burden of MF. T1 mapping does not require gadolinium contrast and provides an insight into the early assessment of diffuse fibrosis, which has been proved to reverse following AVR .The assessment of MF by CMR may in the future refine the selection of asymptomatic patients with severe AS who may benefit from early AVR, although this requires confirmation in larger prospective studies. A prevalence of up to 16% of wild-type transthyretin cardiac amyloidosis was reported in patients with severe AS . Apical Molecular biomarkers related to cardiac fibrosis and remodeling have been tested to find an accurate risk stratification strategy in severe AS patients optimizing the therapeutic decision. Galectin-3 , a profibrotic and pro-inflammatory molecule, regulates apoptosis through interaction with activated K-Ras protein, acts through the Wnt signaling pathway, and modulates cell–ECM adhesion by binding to the main proteins involved in cell adhesion . Gal-3 sIbarrola et al. found that, in AS, the circulating levels of Gal-3 could reflect oxidative stress . Gal-3 dGal-3 has been studied in clinical cardiac settings, although it is not specific for identifying MF and depends on renal function ,66,67. H2/m2, baseline Gal-3 was unrelated to age, symptomatic status, AVA index, LVEF, LV mass index, or valvulo-arterial impedance, and it was negatively correlated with the estimated glomerular filtration rate (eGFR)  [p = 0.3) [Arangalage et al. do not sustain support the use of Gal-3 in the decision-making process for asymptomatic patients with AS . In thei< 0.001) . Gal-3 tp = 0.3) .p < 0.001) in AS patients [On the other hand, Baran et al., prospectively studying moderate-to-severe degenerative AS patients over a 48-month period, reported that the CHF exacerbations were mainly dependent on Gal-3 level, correlating with vascular stiffness parameters . White epatients . Gal-3 mpatients .Ramos et al. recently proposed an integrative medicine approach with multi-disciplinary information in asymptomatic severe AS patients’ evaluation . The autThus, clinical studies reported contradictory results regarding the role of Gal-3 in AS risk stratification and outcome. When this biomarker was studied in combination with other serum biomolecules, the results were more promising . GirithasST2 represents the soluble isoform of the protein suppression of tumorigenicity-2, that inhibits the effects of IL-33/ST2L signaling by acting as a decoy receptor for IL-33 . In parap < 0.0001) and AOA (p = 0.004) in severe AS [sST2 has been studied in severe AS as a promising biomarker. It represents an independent predictor of cardiovascular events in this setting . Circulaevere AS . This bievere AS .Fabiani et al., on the contrary, reported that, although the severe AV patients presented elevated sST2 levels, no correlation was found between these levels and MF—, assessed by interventricular septum biopsy—. sST2 ≥ p < 0.001) [Other authors tried to create a model of multiple biomarkers  to better perform the risk stratification of patients with AS . These b< 0.001) .sST2 is now part of the serum biomolecules proposed by Giritharan et al. to be studied in combination with an imaging biomarker, GLS, in the risk stratification of AS patients .JNK1 , TGF-β receptor 1 and TGF-β receptor 2, and ETS-1 (ETS proto-oncogene 1) [The cardiac fibrosis process is influenced by micro-RNAs (miRNAs) targeting the key molecules, which mediate the transcription of ECM genes and TGFβ signaling . Experimogene 1) .The levels of miRNA-29b , miRNA-2Its myocardial  and plasSerum growth differentiation factor-15 (GDF-15) is increased by aging and in response to cellular stress and mitochondrial dysfunction . StudiesGDF15 predicted a low (<5) Katz score, independent of the relationship with LV mass, age, renal function, or indices of LV dysfunction . GDF-15 Lindman et al. used a model with three biomarkers , which improved the reclassification of severe AS patient risk when added to the STS score . GirithaCollagens, a superfamily of 28 members, are synthesized as procollagens, cleaved to the mature form, and then enzymatically (MMPs) cleaved and released as biologically active fragments . The balHigh serum PICP and PIIINP levels were significantly associated with MF in some studies , althougThe dysregulation of myocardial MMPs and TIMPs starts at an early disease stage, when the LV function is still normal in AS ,109. In Bäz et al. reported that B+/C+ Tenascin-C and MMP-9 changes correlated with LA involvement in severe AS, while TIMP-1, ED-A+ Fn, ET-1, and NGAL changes were associated with the transition to PH with right heart dysfunction . MMP-3 cBrain natriuretic peptide (BNP) is mainly synthesized by LV myocytes as a response to pressure or volume overload. Its precursor is cleaved in BNP, the active amino acid, and N-terminal proBNP (NT-proBNP), an inert amino acid. Clinicians must be aware that the half-life of the most used natriuretic peptides is different: BNP’s half-life is 20 min, while NT-proBNP’s half-life is 90–120 min . BNP synThe natriuretic peptides help perform risk stratification for AS patients regarding heart failure, syncope, and sudden cardiac death ,120,121.A higher NT-proBNP ratio NT-proBNP divided by the upper limit of normal NT-proBNP for age and sex) predicted mortality in more valvular heart diseases with the strongest association detected for AS . A higheWeber et al. calculated a baseline NT-proBNP cut-off of 640 pg/mL, which was discriminative for an adverse outcome in severe AS patients, especially in the conservative treatment approach . Higher High-sensitivitytroponin T (hsTnT) adds information to NT-proBNP as a routinely available biomarker for risk stratification concerning post-operative survival in patients with severe AS admitted for AVR . CardiachsTnT level > 14 pg/mL was associated with ischemic coronary events risk in mild-to-moderate– AS patients , while hStarting from their multi-centric study results, which found the cTnT, NT-proBNP, and GLS combination to be a prognostic tool in symptomatic severe AS patients undergoing TAVI, Perry et al. proposed the same approach for asymptomatic severe AS patients . Some reAnnexin A1, an endogenous anti-inflammatory mediator, was studied in the fibrosis context. In AS, its pericardial level predicted AF in severe AS patients . ActivinOsteopontin (OPN) can induce the activation of p90 ribosomal s6 kinase, Akt, glycogen synthase kinase-3β, NFAT/GATA-4, calcineurin-NFAT, and serum- and glucocorticoid-inducible kinase as a response to pressure or volume overload . BaselinAngiotensin-converting enzyme 2 (ACE2) activity was also studied in the AS context. Although the presence of hypertension and/or antihypertensive therapies can introduce some bias in the analysis, researchers reported a positive correlation between plasma ACE2 activity and LV mass in AS patients. ACE2 was proposed as a marker of early myocardial decompensation in AS because its high plasmatic levels were associated with increased LV diastolic volume but not with LVEF or GLS . CopeptiAS is a disease both of the valve and the myocardium, characterized by fibrosis and calcification of valve leaflets, progressive LV hypertrophy, and myocardial fibrosis. Therefore, a comprehensive assessment of patients with AS is recommended. Beyond the conventional assessment of LV remodeling and ejection fraction, the assessment of LV GLS via STE and myocardial fibrosis estimated via CMR will be increasingly used in the decision-making process in patients with AS in the near future. Such a multi-parametric approach, including biomarkers, can have a role in defining the optimal timing for intervention in apparently asymptomatic severe AS patients and stratifying the risk in patients undergoing AVR. However, confirmatory data from randomized clinical trials are awaitedare awaiting publication in order to define their utility in current clinical practice and incorporate them into the management algorithms. A better knowledge of the underlying mechanisms of the transition from LV hypertrophy to LV decompensation may provide an insight into novel mediators of cardiac remodeling and decompensation for possible diagnostic and prognostic use in AS and also identifying the biotargets for novel pharmacological therapies.


AAR and MVO also significantly reduced after 12 weeks. At baseline, there were reasonably moderate correlations between IS and LVEF , LV GLS  and LV GCS  as well as between AAR and LVEF , LV GLS  and weak with LV GCS . At follow-up, only MSI and change in LV GCS over time showed a weak but significant correlation . Patients with larger AAR at baseline improved more in LVEF (p = 0.019) and LV GLS (p = 0.020) but not in LV GCS. Conclusion: The CMR tissue characteristics of myocardial injury correlate with the magnitude of LV dysfunction during the acute stage of STEMI. AAR predicts improvement in LVEF and LV GLS, while MSI is a sensitive marker of LV GCS recovery at three months follow-up after STEMI.Background: Left ventricular global longitudinal strain (LV GLS) is a superior predictor of adverse cardiac events in patients with myocardial infarction and heart failure. We investigated the ability of morphological features of infarcted myocardium to detect acute left ventricular (LV) dysfunction and predict LV functional recovery after three months in patients with acute ST-segment elevation myocardial infarction (STEMI). Methods: Sixty-six STEMI patients were included in the C-reactive protein (CRP) apheresis in Acute Myocardial Infarction Study (CAMI-1). LV ejection fraction (LVEF), LV GLS, LV global circumferential strain (LV GCS), infarct size (IS), area-at-risk (AAR), and myocardial salvage index (MSI) were assessed by CMR 5 ± 3 days (baseline) and 12 ± 2 weeks after (follow-up) the diagnosis of first acute STEMI. Results: Significant changes in myocardial injury parameters were identified after 12 weeks of STEMI diagnosis. IS decreased from 23.59 ± 11.69% at baseline to 18.29 ± 8.32% at follow-up ( Despite impressive advances in diagnosis and management over the last decades, ST-segment myocardial infarction (STEMI) continues to be a major public health problem in the Western world and is becoming an increasingly important issue in developing countries ,2. TimelLeft ventricular (LV) remodelling after STEMI can be induced by several factors, the first of which is the extent of myocardial injury ,5. EarlyAccumulating evidence suggests that markers of inflammation may be reliable indicators of the extent of myocardial injury and increased cardiovascular risk . A recenAlthough echocardiography remains the first-choice imaging modality in acute STEMI settings, cardiovascular magnetic resonance (CMR) imaging allows for a more detailed characterization of cardiac structure . CMR proThe main objective of our study was to investigate whether the CMR-derived morphological changes of myocardial tissue during acute injury are associated with LV functional parameters and their change at three months follow-up after STEMI.This prospective, observational CMR study is a sub-study of CAMI-1  trial  [2, reconstructed voxel size = 1.6 × 1.6 × 8.0 mm3, and 25–30 phases per cardiac cycle. T2-weighted images were obtained using fast-tau inversion-recovery fast spin-echo sequence in identical locations to LV short-axis cine images. Finally, a T1-weighted 3-dimensional (3D) contrast-enhanced inversion-recovery gradient-echo sequence was used for late gadolinium enhancement (LGE) image acquisition. Images were obtained 10 min after injection of 0.1 mmol/kg gadobutrol .CMR studies were performed with onsite available MRI scanners with two different field strengths: 1.5T  and 3T (Siemens Skyra and Philips Signa HDxt). Cine images were acquired using a retrospectively gated balanced steady-state free precession (bSSFP) sequence with multiple breath-holds at end-expiration in three LV long-axis  planes and a stack of short-axis slices covering the entire LV. The typical bSSFP sequences parameters were as follows: repetition time = 3.5 ms, echo time = 1.7 ms, flip angle = 60°, field of view = 420 × 420 mmCMR studies were anonymized and analysed centrally in a blinded manner by experienced observers at MRI-Core-Lab . Images were analysed offline using commercially available software . LV volumes, LV myocardial mass, and LV ejection fraction (LVEF) were quantified according to the CMR consensus paper for LV function and mass quantification . LV end-LV myocardial deformation analysis was performed using the CMR feature tracking (FT) technique. Three LV long-axis  and three LV short-axis  cine images were uploaded into QStrain, version 2.0 module. LV endocardial and epicardial borders were contoured by a point-and-click approach at the LV end-diastolic phase. After the application of a tissue tracking algorithm, endocardial and epicardial borders were detected through all cardiac phases. If the contouring was inaccurate, borders were manually adjusted, and the tracking algorithm was repeated to ensure correct endocardial and epicardial surface delineation and precise myocardial strain measurements. The right ventricular upper septal insertion point was manually indicated to allow for accurate LV segmentation according to an AHA 16-segment model . LV globThe endocardial and epicardial contours drawn on cine images were transferred into T2-weighted and LGE images to estimate myocardial oedema, necrosis/scar area, and calculate area-at-risk (AAR), infarct size (IS), microvascular obstruction (MVO) size, and myocardial salvage index (MSI). The extent of myocardial oedema and myocardial necrosis/scar area was calculated using the signal threshold versus reference mean (STRM) > 3 standard deviations (SD) method as it provides the greatest accuracy with acceptable reproducibility compared to other signal intensity threshold techniques ,20. All t-test or Wilcoxon test was used as appropriate to compare continuous variable differences between baseline and follow-up. Delta (∆) LVEF, LV GLS, and LV GCS were defined as changes from baseline to follow-up. Correlations between variables were tested with Pearson‘s product-moment correlation. Patients were further divided into groups based on the IS (<median IS and ≥median IS group), AAR (<median AAR and ≥median AAR group), and MSI (<median MSI and ≥median MSI group). The comparison of the groups was performed using a two-sided, independent-sample Student’s t-test for normally distributed data and the Mann–Whitney test for skewed data. Values of p < 0.05 were considered statistically significant.The statistical analysis was performed using Microsoft Excel and commercially available software . The Shapiro–Wilk test was used to determine whether the data were normally distributed. Body mass index (BMI), follow-up AAR, MVO, MSI, (∆) LV GLS, and LV GCS were not normally distributed. Continuous variables were expressed as mean ± standard deviation (SD) or median ± interquartile range (IQR) as appropriate depending on their distribution. Student‘s paired A total of 66 STEMI patients were finally included in the study. The mean age was 57.5 ± 10.1 years. The youngest patient was 36 years while the oldest was 80 years old. Study participants were predominantly male smokers. The mean time to PPCI was 4.5 h (4.5 ± 2.6 h). More than half of the patients had anterior STEMI, and the majority presented with Killip class 1 on admission. None of the participants had severe heart failure, classified as Killip class 3–4. More detailed clinical characteristics and demographics are shown in Six patients were lost during the follow-up: 1 patient died on day 114 after STEMI, 1 underwent pacemaker implantation and was excluded due to relative contraindication for a CMR scan, 2 patients refused to undergo a second CMR study, and 2 patients were unreachable .p = 0.036) and LVEF improved (p < 0.001). The LVESVi was 41.30 ± 10.99 mL/m2 at baseline vs. 38.61 ± 13.78 mL/m2 at follow-up, while LVEF was 52.45 ± 7.07% at baseline vs. 55.78 ± 7.80% at follow-up. Systolic LV dysfunction (LVEF < 50%) was present in 25 (37.9%) patients at baseline and in 12 (18.2%) patients at follow-up. Severe LV dysfunction (LVEF < 35%) was observed in 1 (1.5%) patient and at both time points. There was a significant improvement in LV GLS at follow-up  as well as in LV GCS .After 12 weeks, there was no significant change in LVEDVi, while LVESVi was significantly reduced (p < 0.001). AAR and MVO also significantly reduced after 12 weeks: AAR 37.19 ± 14.79% at baseline vs. 1.44 ± 7.08% at follow-up (p < 0.001) and MVO 1.04 ± 2.79% at baseline vs. 0.0 ± 0.0% at follow-up (p = 0.004). All functional and morphological CMR parameters at baseline and follow-up are listed in MVO was present in 25 patients (37.9%) during the acute STEMI phase. Interestingly, 5 (7.6%) patients maintained hyperintense signal on T2-weighted images during follow-up, which might be considered residual myocardial oedema. Significant changes in myocardial injury parameters were identified after 12 weeks of STEMI diagnosis. IS decreased from 23.59 ± 11.69% at baseline to 18.29 ± 8.32% at follow-up , while LV GLS  and LV GCS  were correlated positively with IS. AAR and LVEF  were also negatively correlated, whereas LV GLS  and LV GCS  showed a positive correlation with AAR.At baseline, there was a moderate negative correlation between IS and LVEF . At follow-up, only MSI and change in LV GCS over time showed a weak but significant correlation . More details are summarized in The correlations between MSI and LV functional parameters were non-significant (p = 0.019) and LV GLS (p = 0.020) but not in LV GCS (p = 0.008) , AAR , and MSI . Analysis showed that patients with larger IS at baseline had lower LV functional parameters—LVEF, LV GLS, LV GCS, and vice versa . There wn LV GCS . In cont= 0.008) . InteresThe main purpose of our study was to determine whether the CMR features of tissue characterization  are accurate predictors of LV functional recovery  after three months following acute STEMI.AAR (quantified using T2-weighted images) and IS (quantified using LGE images) predict LVEF and LV GLS but not LV GCS improvement after STEMI;Acute myocardial injury characteristics quantified by CMR correlate with the extent of LV systolic dysfunction in the acute STEMI phase;MSI is associated with improvement in LV GCS after acute STEMI.Our study findings can be summarized as follows:As described above, the myocardial area-at-risk was quantified using T2-weighted images in our study. We found that only a quantitative assessment of AAR was able to predict LV functional recovery (improvement in LVEF and LV GLS) after three months. Similar to a recent study of 50 subjects, there was a good agreement and correlation between AAR measurements, ECV, and T1 mapping values . DespiteNumerous studies have established an independent link between hyperglycaemia and adverse outcomes in patients with acute coronary syndromes. High blood glucose levels negatively influence coronary circulation and myocardial tissue through various pathophysiological mechanisms, such as cellular harm, programmed cell death, and compromised endothelial function . Strict More than two decades have passed since CMR imaging using the LGE technique enabled us to discriminate between irreversibly injured and viable myocardium . In patiInterestingly, in the same study of 103 subjects with STEMI, authors found that myocardial injury quantified during the hyperacute phase using the LGE technique, predicts late LVEF recovery and adverse cardiovascular events . HoweverNovel CMR techniques, such as parametric mapping, might improve tissue characterization during acute myocardial injury. Pankaj et al. demonstrated that LGE imaging overestimates the IS during the acute phase of myocardial infarction compared with ECV fraction, which has been shown to have a superior agreement with IS estimated at follow-up scans . AccordiMSI is a powerful marker of PPCI success and can be used as an endpoint in cardioprotective clinical studies . The extOur analysis demonstrated that MSI correlates better with the LV GCS change than LV GLS or LVEF. This is likely to be influenced by the larger extent of affected, oedematous, but non-infarcted myocardium that is expected to improve in systolic function after three months. The LV GLS reflects the shortening of subendocardial fibres and is first affected during myocardial ischemia with less ability to improve if myocardial necrosis occurs.Our results support the previous research, showing that MSI is a reliable predictor of LV functional recovery and adverse LV remodelling ,37. In aThe ability of LVEF to stratify the risk of future cardiac events in patients with STEMI is limited. Previous studies showed that for a period of two years after STEMI, 67% of cardiac deaths occurred in patients with LVEF > 35%, while ventricular tachycardia was observed only in 8% of patients with reduced LVEF ,38. AccoThus, despite primary and secondary prevention, high-risk patients remain unidentified. It is particularly important to include structural and functional  CMR parameters in the routine clinical risk stratification model . LV GLS The individual risk assessment is the next step in personalized healthcare. The ability to predict adverse cardiovascular events using multiple CMR imaging biomarkers will significantly impact the decision-making process to achieve better care for patients with STEMI. Ongoing studies are focused on developing precision models using machine learning and will serve as a clinical decision support system to improve patient outcomes and assist healthcare providers .Our study is limited due to the small sample size, and a larger population could increase the strength of our research. Unfortunately, not all CMR scans were suitable for complete analysis, and not all patients underwent follow-up CMR. The parametric mapping was not performed in our cohort, as the mapping technique was unavailable in all participating centres. The inclusion of parametric mapping would certainly improve the prediction of LV functional recovery. We included only hemodynamically stable patients without significant comorbidities.Moreover, the rate of advanced heart failure was relatively low; thus, our cohort cannot reflect the actual STEMI population. In addition, quantification of the IS may vary depending on the form, dosage, and timing of the contrasting agent after injection, as well as the timing after acute STEMI. Lastly, longer follow-up intervals might be beneficial in order to achieve complete LV recovery and remodelling.The CMR tissue characteristics of myocardial injury  correlate with the LV dysfunction’s magnitude during the acute stage of STEMI. AAR predicts improvement in LVEF and LV GLS, while MSI is a sensitive marker of LV GCS recovery at three months follow-up after STEMI. As the reduction in CRP levels provides smaller infarcts and better cardiac function , this could be considered an additional therapeutic option in STEMI.