At present, there is no early prediction model of left ventricular reverse remodeling (LVRR) for people who are in cardiac arrest with an ejection fraction (EF) of ≤35% at first diagnosis; thus, the purpose of this article is to provide a supplement to existing research.A total of 109 patients suffering from heart attack with an EF of ≤35% at first diagnosis were involved in this single-center research study. LVRR was defined as an absolute increase in left ventricular ejection fraction (LVEF) from ≥10% to a final value of >35%, with analysis features including demographic characteristics, diseases, biochemical data, echocardiography, and drug therapy. Extreme gradient boosting (XGBoost), random forest, and logistic regression algorithm models were used to distinguish between LVRR and non-LVRR cases and to obtain the most important features.There were 47 cases (42%) of LVRR in patients suffering from heart failure with an EF of ≤35% at first diagnosis after optimal drug therapy. General statistical analysis and machine learning methods were combined to exclude a number of significant feature groups. The median duration of disease in the LVRR group was significantly lower than that in the non-LVRR group (7 vs. 48 months); the mean values of creatine kinase (CK) and MB isoenzyme of creatine kinase (CK-MB) in the LVRR group were lower than those in the non-LVRR group . Moreover, AUC values for our feature combinations ranged from 97 to 94% and to 87% when using the XGBoost, random forest, and logistic regression techniques, respectively. The ablation test revealed that beats per minute (BPM) and disease duration had a greater impact on the model’s ability to accurately forecast outcomes.Shorter disease duration, slightly lower CK and CK-MB levels, slightly smaller right and left ventricular and left atrial dimensions, and lower mean heart rates were found to be most strongly predictive of LVRR development (BPM). Angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB), β-blockers, and mineralocorticoid receptor antagonists (MRA) are considered the cornerstone for the treatment of patients suffering from heart failure with reduced ejection fraction (HFrEF), as these approaches can facilitate left ventricular reverse remodeling (LVRR), minimize the hospital admission rate of patients with heart failure (HF), and decrease the overall rates of mortality and cardiovascular mortality, including those related to sudden cardiac death (SCD) –5. In paThis study was a one-center retrospective research study. Clinical data were collected from 265 consecutive inpatients who were first diagnosed with an EF of ≤35% (HFrEF) in the Affiliated Zhongshan Hospital of Dalian University from March 2018 to March 2020, with multiple follow-up records collected for each patient. Patients suffering from cardiomyopathy with possible spontaneous LVRR, such as patients suffering from tachycardia-induced cardiomyopathy, perinatal cardiomyopathy, myocarditis, and alcoholic dilated cardiomyopathy, were excluded  to enrollment in the study, while the onset of symptoms of heart failure was defined as the change of NYHA classification in patients’ daily lives. The final echocardiogram taken prior to study commencement was considered the patient’s basic echocardiography.The drug therapy for HF was optimized in the ward based on clinical guidelines following baseline assessment . The treA technician attached to the cardiovascular ultrasound department performed all echocardiography according to international guidelines. The left ventricular end-diastolic width was fitted in the para long-axis M-mode guided by the 2D echo. In the sinus rhythm, the left ventricular volume was measured at apex four and two ventricles using the Simpson method. In the non-sinus rhythm, the left ventricular mass was measured in five cycles and then averaged. The left ventricular end-diastolic diameter and the capacity were indexed by body surface area. LVEF was obtained with reference to the changes in the left ventricular volume.Follow-up appointments for patients were made as required. The visits ended in February 2021, upon heart transplantation, or on the date of death. Transthoracic echocardiography was performed during all visits. LVRR was defined as an absolute raise in LVEF from ≥10% to a final value of >35%, lasting up to the final visit. Non-LVRR was well-defined as a total upsurge in the left ventricular ejection portion of <10% or with a final value of <35%, or a reduction in the left ventricular end-diastolic diameter of <10% for all visits except for those less than 1 year. Patients who failed to meet the criteria of LVRR and had the final visit within 1 year were excluded.U test and the chi-square test, which are autonomous t-tests.The data were presented as the mean normal deviation for generally distributed variable quantities and median SD for those with a non-normal distribution . Heterogeneity in the variance was discovered by means of a left rotation test, which had an alpha value of <0.05. Different groups were classified using the Mann–Whitney max for the extreme value of a variable, and xmin for the smallest value of a variable):A total of 53 samples were collected for examination; details are presented in via 10-fold cross-authentication. Nine of these subsets were used for training, while one was used for testing; this process was carried out a total of 10 times to guarantee that each subset was tested. Finally, all results were averaged to measure the model performance. The specific experimental process is illustrated in via an ablation analysis, which is the process of setting up a control group by removing a factor and then measuring the importance of that factor based on the subsequent degree of decline in the experimental results.In order to conduct a model research, we used XGBoost, random forest, and logistic regression . XGBoostFeature assortment was performed to find the optimal feature grouping in the forecast model. The distribution of all 53 features is shown in The selected features were all greater than zero in terms of importance. The greedy search started with an empty set of important features. The selection was performed according to the following iterative process: first, the feature with the highest AUC values to the set of important features was added; then, the next feature that causes the AUC to reach the highest value in the set of the remaining features to the set of important features was found; this process was repeated until there are no remaining features or there is no increase in the AUC value of the set of important features, thus establishing the final prediction model.A total of 378 clinical data points were collected from 109 inpatients. The LVRR was identified in 47 (45.2%) of the 109 examined patients . The disThe scikit-learn 0.24.2 software package was used to perform machine learning in the Python 3.9.1 tool environment. Moreover, the SPSS 26.0 software  was used for statistical analysis.A total of 35 features were screened out through the tree model. Classification ability tests with or without improvement were performed on each of the 35 features, with the results shown in Our main findings in this study were as follows  is associated with the elevated left atrial pressure and its spread to the pulmonary circulation, while HFrEF may be associated with pre- and post-capillary pulmonary arterial hypertension. Compared with the control group (1.4%/mmHg), patients with HFrEF or HFpEF (0.8–0.9%/mmHg) had a moderately lower vascular elastic dilation coefficient  might better predict the LVRR . CMR is The random forest and XGBoost algorithms were found to perform very well at forecasting LVRR in people with HFrEF. The LVRR of HFrEF could be predicted using a combination of conventional laboratory testing and echocardiographic indices. These machine learning classifiers can aid in achieving precise managing and danger assessment for people with HFrEF.The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.The studies involving human participants were reviewed and approved by Ethics Committee of Affiliated Zhongshan Hospital of Dalian University. The patients/participants provided their written informed consent to participate in this study.LL and CQ: conception and design of the research and writing of the manuscript. HQ, X-RW, X-YZ, Y-OW, and X-MY: acquisition of data. LL, CQ, and J-RZ: analysis and interpretation of the data. J-RZ and JQ: statistical analysis. S-LZ and JQ: critical revision of the manuscript for intellectual content. All authors read and approved the final draft.


Cardiac rhythm abnormalities, such as atrial fibrillation (AF) and ventricular tachycardia (VT)/ventricular fibrillation (VF), account for a significant proportion of adverse cardiac events and mortality . In factSaadeh and Fazmin review the mechanisms by which age-related mitochondrial dysfunction promotes arrhythmic triggers and substrate. This provided insights into novel potential anti-arrhythmic pharmacological interventions that specifically target upstream mitochondrial function, and hence ameliorates the need for therapies targeting downstream changes which have constituted traditional antiarrhythmic therapy. Deng et al. reviews the key role of uric acid in mediating oxidative stress and inflammation, which underlie fibrotic change of the atria predisposing to AF. Fong et al. conducted a meta-analysis into modulated calcium homeostasis and calcium release events in AF, demonstrating higher sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) expression in the between primary diseased AF group, but lower expression in the secondary AF groups. Costa et al. describe in-depth the molecular interactions between sex hormones and the cardiac ion channels, as well as the clinical implications of these interactions on the cardiac conduction system, in order to understand the link between these hormones and the susceptibility to cardiac arrhythmias.Cellular, animal and computational models have been used to study the molecular and electrophysiological mechanisms underlying cardiac arrhythmias . Saadeh Avula et al. presented APD dispersion data from two-dimensional optical mapping in a mouse model with F1759A SCN5A overexpression modeling long QT syndrome type 3. They then presented theoretical models for APD dispersion, methods for analysis and calculation of APD dispersion, and showed that APD dispersion in clustered patterns is the predominant configuration for spontaneous occurrence and persistence of AF and VF. Liu et al. conducted experiments to examine the effects of autonomic input in vein of Marshall-mediated AF. They found that electrical stimulation of the left superior ganglionated plexi shortened atrial refractoriness, increased APD dispersion and the vulnerability window. These effects were prevented by low level stimulation or ethanol ablation of the vein of Marshall, or muscarinic blockade by atropine. Acquired causes of VT/VF may arise from remodeling after myocardial infarction. In a mouse model with knockout of the CC chemokine receptor 9 (CCR9), abnormalities in ion currents, calcium handling, gap junction and action potential conduction were prevented, suggesting that the CCR9 can be a promising therapeutic target for reducing the likelihood of myocardial infarction-related arrhythmias .via the development of ischemic stroke .AF is the commonest cardiac rhythm abnormality observed in clinical practice and accounts for significant morbidity and mortality c stroke , dementic stroke , 8 and hc stroke . Shang eKim, Yu, Kim, Lee et al.), demonstrating that in patients with normal left ventricular ejection fraction, high H2FPEF score and increasing age were independently associated with the development of ischemic stroke. Song et al. found that a comprehensive evaluation of serum uric acid and B-type natriuretic peptide levels, left atrial diameter and left ventricular ejection fraction can stratify the risk of stroke in patients with non-valvular AF. A large retrospective cohort study conducted propensity score matching between with atrial flutter and AF . Among patients without history of stroke, the risk of dementia was higher in patients with AF than in patients with AFL.One of the most devastating outcomes of AF is stroke for which the CHA2DS2-VASc score has been used for its risk stratification . A recenPeng et al.). patients with short episodes of AF <24 h were compared to those with 24 h or longer in a propensity score-matched analysis for cryoablation of pulmonary veins isolation . Higher success rate and lower incidence of stroke/transient ischaemic attacks were observed for the <24 h group compared to the ≥24 h group during follow-up. Recurrence in AF remains a problem despite improvement in ablation technology. A prospective cohort study found that leukocyte telomere length predicted disease progression from paroxysmal to persistent AF following catheter ablation . Soluble Suppression of Tumorigenicity 2, was shown to be predictive of AF recurrence after radiofrequency ablation in patients with persistent AF . A systematic review and meta-analysis found that the HAS-BLED score has moderate predictive abilities for bleeding risks in patients with AF regardless of type of oral anticoagulants . For medical treatment of AF, beta blockers are frequently used. Interestingly, beta blockers consistently decreased long-term mortality in patients with high-burden and low-burden of premature atrial complexes, and this effect appears not to be mediated through a reduction in AF or new onset stroke . Recent work has explored traditional Chinese medicine as an adjunct therapy .The following studies investigated the impact of interventional and medical treatment on outcomes in patients with AF. Balloon-based catheter ablations, including hot balloon ablation and cryoballoon ablation, have rapidly emerged as alternative modalities to conventional catheter ablation owing to their procedural advantages and better clinical outcomes and safety profiles. A recent study found that patients undergoing hot balloon ablation had a higher incidence of touch-up ablation and longer procedural time, but with comparable clinical outcomes on mid-term follow-up . In a propensity score-matched study between patients undergoing transcatheter and surgical aortic valve replacement, post-operative AF had a worse impact on heart failure-related hospital admissions and composite outcome of mortality, stroke and heart failure-related admissions . In a single center prospective study, machine learning models were developed using least absolute shrinkage and selection operator (LASSO) and random forest (RF) algorithms for variable selection . Their LASSO-Cox model showed an area under the curve of 0.84 for predicting 1-year mortality.A registry study from Shanghai, China investigated the impact of new onset AF in patients with acute myocardial infarction. Interestingly, the authors found that asymptomatic rather than symptomatic new onset AF was significantly predictive of cardiovascular mortality and all-cause mortality . Another study from the same group examined a large cohort of 4,873 patients undergoing the head-up tilt test, finding that direct drug potentiation is safe and sensitive for diagnosing vasovagal syncope . Patients with an overlap syndrome between chronic obstructive pulmonary disorder and obstructive sleep apnoea showed higher rates of cardiac arrhythmias  compared to those with either condition alone . Heart rate was shown to be predictive of all-cause mortality in patients suffering from multiple myeloma, but further work is needed to explore the prognostic role of cardiac arrhythmias in this condition . Li and Zhang developed an autodetection algorithm using neural network combined with the attention-based bidirectional long-short term memory model for classifying nine different types of ECG patterns, including normal electrocardiogram, atrial fibrillation, atrioventricular block, left bundle branch block, right bundle branch block, premature atrial complexes, premature ventricular complexes, ST depression and ST elevation (Li and Zhang). Regarding AF treatment, the H2FPEF Score, which reflects the degree of left ventricular diastolic dysfunction, was improved following catheter ablation . Zhang et al. compared the catheter ablation to pacing in patients with tachycardia-bradycardia syndrome, reporting lower rates of the composite endpoint of cardiovascular-related hospitalization and thromboembolic events, as well as the progression of atrial fibrillation and heart failure.Age was identified as a risk factor of syncope recurrence in elderly patients with vasovagal syncope and positive head-up tilt test . Another study from the same group investigated whether the obesity paradox in all-cause mortality is present among the Chinese population with an ICD but did not demonstrate its presence . Sun et al. found that compared to night-time heart rate of ≤ 50 or ≥70 bpm, heart rate between 50 and 70 bpm was associated with lower risks of ventricular tachyarrhythmias, appropriate ICD shocks, inappropriate ICD shocks, and all-cause mortality. A retrospective study from Hong Kong, China investigated Chinese patients who were hospitalized for acute heart failure, demonstrating that fragmented QRS was a significant predictor of VT/VF, sudden cardiac death and cardiovascular mortality .VT/VF can arise from acquired causes, such as ischaemic heart disease, electrolyte disturbances and drugs. van der Voorn et al.). The commonest ion channelopathy globally is long QT syndrome, which is more common in Western compared to Asian populations  has aided risk stratification although its sensitivity, specificity, positive predictive value and negative predictive value can differ depending on the protocols employed (Brugada syndrome (BrS) is characterized by coved or saddle-shaped ST segment elevation in the right precordial leads . It has employed . Recent employed .Monasky et al. evaluated the role of genetic testing for risk stratification in BrS. They recommend that whole exome or whole genome testing and family segregation analysis should always be performed. Chen X. et al. studied the clinical and genetic characteristics of 104 probands with early repolarization syndrome, reporting its association with loss-of-function genetic defects in genes encoding the cardiac calcium channel. They identified a unique clinical entity characterized by decreased heart rate and QTc, as well as increased transmural dispersion of repolarization. In the case of the CACNA1C-P817S variant, impaired trafficking of the channel to the membrane contributes to the loss-of-function in the calcium channel.Nevertheless, recent available evidence indicates that risk prediction is more accurate when a multi-parametric approach rather than rely on a single investigative method . MonaskyWang Y. et al.). The pre-treatment baseline QTcd were significantly longer in responders treated with metoprolol compared to non-responders and that it was negatively correlated with SS after metoprolol treatment. The prenatal management for immune-associated congenital heart block in fetuses was reviewed, in particular issues pertaining to clinical management, including the roles of autoantibodies in its pathophysiology, diagnosis and prognosis . A study of multiple myeloma patients from Xi'an, China found that approximately half of the patients suffered from cardiac arrhythmias . In particular, those with sinus bradycardia had lower incidences of all-cause mortality compared to those without it.Finally, several studies examined risk stratification strategies for other tachycardias and also bradycardias. For example, the role of baseline-corrected QT interval dispersion (QTcd) in predicting the effectiveness of metoprolol in pediatric postural tachycardia syndrome was examined  and Tianjin Key Medical Discipline  Construction Project.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.


The most-commonly used multi-slice Simpson's method employed with routine two-dimensional segmented cine images makes it difficult to evaluate left ventricular (LV) volume and function due to endocardial border blurring and beat-to-beat variation during atrial fibrillation (AF) status.To assess the feasibility of compressed sensing real-time (CSRT) cine imaging combined with an area-length method for quantification of LV systolic function in normal sinus rhythm (NSR) and AF.n = 36) or AF (n = 35). Image quality and edge sharpness for both sequences were assessed. The LV functional measurements in patients with NSR included end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), cardiac output (CO), cardiac index (CI), and LV mass (LVM); all were assessed using segmented cine with Simpson's rule in short axis  and area-length (AL) method in the two chamber (Seg2CH_AL) or four chamber (Seg4CH_AL) and CSRT cine with AL method in the two chamber (CSRT2CH_AL) or four chamber (CSRT4CH_AL). Finally, the mean, maximum, and minimum values of each LV functional parameter [EDV/ESV/SV/EF/CO/CI/LVM/heart rate (HR)] from 4~5 consecutive heartbeats were measured using CSRT2CH_AL in patients with AF.The CSRT cine sequence and routine segmented balanced Steady-State-Free-Precession cine sequence were performed in 71 patients with NSR (p > 0.05), ESV (p > 0.05), SV (p > 0.05), EF (p > 0.05), and LVM (p > 0.05) assessed with CSRT2CH_AL did not differ significantly from those obtained with SegSA_Simpson. In patients with AF, CSRT image quality score (p < 0.001) and edge sharpness (p < 0.001) both were significantly higher than those obtained from segmented cine. The CSRT2CH_AL provided significantly different results among mean, maximum, and minimum values of each LV parameter from 4~5 consecutive heartbeats  with strong inter- and intra-observer agreement in AF.In patients with NSR, measurements of EDV (The CSRT cine sequence combined with two chamber area-length analysis accurately assessed LV systolic function in NSR. This approach is expected to permit the assessment of multiple parameters in consecutive heartbeats with good inter- and intra-observer reproducibility for beat-to-beat analysis of LV function in AF. Cardiovascular magnetic resonance imaging (CMR) is well recognized as the “gold standard” for quantification of cardiac function –3. The SReal-time cine imaging combined with compressed sensing (CS) using a highly under-sampled k-space and a non-linear iterative reconstruction algorithm can provide spatiotemporal resolution in a range similar to that obtained with segmented cine –13. The Thus, the aim of this study was to evaluate the image quality of a compressed sensing real-time cine sequence and its feasibility for quantification of LV systolic function by the AL method in patients with NSR and AF.A total of 71 consecutive patients with a variety of cardiac diseases with NSR , 44.2 ± 14.5 years) or sustained AF  were enrolled in this study from May 2021 to September 2021. The persistence of AF was confirmed prior to the magnetic resonance imaging examination. The exclusion criteria for this study included cardiac implantable electronic device, claustrophobia, and other contraindications for CMR. Also excluded were patients who had an asymmetric left ventricle, which was defined as a ratio of septal-lateral to anterior-inferior diameter or of anterior-inferior to septal-lateral diameter exceeding 1.5, as determined in previous ultrasound or CMR short axis end diastole cine images  using 18-channel surface phased array coils. Each subject underwent CMR scanning using a reference segmented (Seg) bSSFP cine sequence and a compressed sensing real-time (CSRT) bSSFP cine sequence during breath-holding; the two sequences were performed in random order. The CSRT sequence used in this study is a product sequence using prospective ECG gating, and its acquisition window is set to 6 seconds for covering several heartbeats. One two-chamber (2CH) slice, one four-chamber (4CH) slice, and a stack of eight to twelve short axis (SA) slices covering the whole LV from mitral valve to apex were acquired with the segmented sequence. Then, the same two long-axis slices and one short axis slice in the midventricular level (located at the same slice location as the reference sequence) were acquired with the CSRT sequence. The details of the imaging parameters for the two sequences are listed in For all qualitative and quantitative analyses, the first 10 phases (lasting about four hundred milliseconds) of the CSRT cine were discarded because of the lack of dummy scans. For both sequences, three location matched slices  were used to evaluate the image quality graded by two senior cardiovascular radiologists with more than 15 and 10 years of CMR experience respectively. Image quality scores were based on the border of myocardium and artifacts, and was graded using a 4-point Likert-type scale, as follows: 1 = nondiagnostic quality; 2 = fair quality, acceptable with some artifacts; 3 = good quality, few artifacts, diagnostic; and 4 = excellent quality, no artifacts. The two long axis and one midventricular SA slices were reviewed individually and an average image quality score was obtained as overall image quality for each sequence.−1) was defined as the inverse of the distance (mm) between the positions corresponding to 20% and 80% of the difference between the maximum and minimum signal intensities along the line drawn perpendicularly to the mid-cavity interventricular septum border with the LV blood pool on the end-diastole four-chamber view , end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), cardiac output (CO), cardiac index (CI), and LV mass (LVM) were performed using dedicated CMR postprocessing software . For all patients with NSR, the 5 methods used for functional assessment were as follows: CSRT cine images combined with AL method in 2CH (CSRT2CH_AL) or 4CH (CSRT4CH_AL), segmented cine images combined with AL method in 2CH (Seg2CH_AL) or 4CH (Seg4CH_AL), and segmented cine images combined with Simpson's rule in SA (SegSA_Simpson) . The AL ame view , 18. In ame view . For allt-test. For EDV, ESV, SV, EF, and LVM derived from each of the above five methods in patients with NSR or the mean, maximum, and minimum values of each EDV, ESV, SV, EF, CO, CI, HR, or LVM from the 4~5 consecutive heartbeats in patients with AF, the two-way analysis of variance (ANOVA) test with post hoc least significant difference (LSD) tests or Friedman test with post hoc LSD tests was applied for comparisons, depending on data normality. The ICC, linear regression, and Bland-Altman analysis were used to assess correlations and agreements between SegSA_Simpson and CSRT2CH_AL or CSRT4CH_AL in patients with NSR. Intra- and inter-observer reproducibility of CSRT2CH_AL and CSRT4CH_AL were assessed in twenty randomly selected patients with NSR. Intra- and inter-observer reproducibility by ICC of mean, maximum and minimum values of each functional parameter from 4~5 heartbeats were assessed in all AF patients. p values <0.05 were considered significant. All data were analyzed using IBM SPSS version 23 and Prism statistical software package .Continuous variables are presented as mean ± SD, or as median  if not normally distributed. Categorical variables are presented as numbers (percentages). The Shapiro-Wilk test was applied to test for normally distributed data. The interobserver agreement of image quality was determined by the intraclass correlation coefficient (ICC). For both sequences, statistical effects on image quality were determined using the Wilcoxon matched-pairs signed rank test. Statistical effects on edge sharpness were determined using the paired p < 0.001).Seventy-one patients successfully completed CMR scans in the present study. Demographic data are listed in p < 0.001). In contrast, in all 35 AF patients, the CSRT cine image quality was higher than that of the segmented cine . In all 71 patients (including both NSR and AF), there was no significant difference in image quality between CSRT and segmented cine . All images of both sequences in NSR and CSRT sequence in AF were regarded as diagnostic images, but almost half of the AF patients (17 of 35) had a segmented cine image quality score lower than 2 (nondiagnostic). Interobserver agreements for the image quality regarding segmented cine and CSRT cine from all patient data were 0.870 and 0.872 (in NSR), 0.943 and 0.934(in AF), respectively. Representative images from the two sequences in patients with NSR and AF are provided in In all 36 patients with NSR, the segmented cine image quality score was higher than that of the CSRT cine . In contrast, in all 35 AF patients, the edge sharpness of the CSRT cine was higher than that of the segmented cine . In all 71 patients (including both NSR and AF), there was no significant difference between the segmented cine and CSRT cine .In all 36 patients with NSR, the edge sharpness of the segmented cine was higher than that of the CSRT cine  between CSRT4CH_AL and SegSA_Simpson. The ICC value for each LV functional parameter compared between CSRT2CH_AL and SegSA_Simpson was better than that between CSRT4CH_AL and SegSA_Simpson  using the CSRT2CH_AL method. There were significant differences among the mean, maximum, and minimum values of each parameter (EDV/ESV/SV/EF/CO/CI/LVM/HR) in the acquired 4~5 consecutive heartbeats. The three new quantitative indices for each functional parameter in patients with AF are summarized in The ICCs of quantitative LV functional data in patients with NSR and AF are summarized in This prospective study was based on a 71-patient cohort including patients with various cardiac disease with NSR or AF. The results demonstrated that a CSRT cine CMR yielded slightly worse scores for image quality and edge sharpness, compared to a standard cine CMR, in patients with NSR. In contrast, in patients with AF, the image quality and edge sharpness of a CSRT cine CMR both were higher than those of a segmented cine. Compared to a segmented cine using Simpson's method, a CSRT bSSFP sequence using the AL method in 2CH was shown to be an accurate method for measuring global LV parameters, including EDV, ESV, SV, EF, and LVM, in patients with NSR. In patients with AF, the CSRT2CH_AL method provided significantly different results among mean, maximum, and minimum values for each LV functional parameter over multiple consecutive heartbeats, while exhibiting excellent inter- or intra-observer reproducibility. In addition, the CS real-time cine acquisition was more timesaving than multi-breath-hold segmented cine acquisition, and may be particularly beneficial for ill patients who cannot hold their breath or tolerate long-duration scans.In the segmented cine sequence, using ECG gating for data synchronization, the raw data of the integrated k-space is acquired segmentally in relatively narrow time windows  for reconstruction of multiple-image frames (cardiac phases) representing the cardiac cycle. This process is repeated over multiple heartbeats to fill the entire k-space for each cardiac phase , 21. Thiin vitro study of cross-sectional echocardiography, that the volume of the symmetric left ventricle can be quantified reliably using an AL method , the 4CH long-axis view is prescribed from the 2CH long-axis view through the apex and center of the mitral and tricuspid valves . SubsequIn clinical practice, LV EF, which is still the most widely used parameter of LV systolic function, has an important prognostic value for multiple kinds of cardiac disorders, including AF . In patiOur study had some limitations. Firstly, because there is no consensus on systolic measurements in AF, we did not find a “gold standard” to verify quantitative functional measurements in patients with AF in our study. Secondly, image edge sharpness was not assessed for every phase of the two cines, given the large number of the phases and the time-consuming nature of the process. The endocardial border-blurring in the routine segmented cine images appear to be more serious and to occur more frequently in phases during cardiac systolic periods in patients with AF. Thirdly, we only calculated functional parameters for 4~5 consecutive heartbeats, given that our study did not use CSRT cine sequences of longer duration. In the future, along with the faster reconstruction and the larger storage space, the acquisition of longer-duration CSRT cine sequences would be more useful for beat-to-beat analysis of LV function in patients with AF. Lastly, we discarded the first 10 phases of each CSRT cine when performing qualitative and quantitative analyses, given our lack of dummy scans. In the future, the sequence designer can provide a choice for user to define a dummy-scan duration of several hundreds of milliseconds or of a number of heartbeats.The CSRT cine sequence provided improved image quality and edge sharpness in patients with AF. This approach also permitted accurate and convenient assessment of the LV systolic function by the two-chamber area-length method in patients with NSR. Furthermore, the CSRT cine imaging combined with two-chamber area-length method facilitated the determination of LV functional parameters in consecutive heartbeats with great inter- or intra-observer reproducibility for beat-to-beat analysis of LV function in patients with AF.The datasets used or analyzed during the current study are not publicly available due to regulatory restrictions. Data that support the findings of this study are available from the corresponding author on reasonable request.The studies involving human participants were reviewed and approved by Ethics Committee of Fuwai Hospital. The patients provided their written informed consent to participate in this study.GY: design of the work, data acquisition, the analysis, interpretation of data, and drafting of the manuscript. CC: design of the work, data acquisition, analysis and interpretation of data, and revision of the manuscript. JA: design of the work and revision of the manuscript. KZ: statistical analysis and revision of the manuscript. KY, XC, and ML: analysis and interpretation of data and revision of the manuscript. SL: data acquisition and statistical analysis. XY: data acquisition and MATLAB script compiling. JW, ZD, SY, and JH: data acquisition. SZ: design of the work and revision of the manuscript. All authors read and approved the final manuscript.The study was supported by National Key Research and Development Program of China under Award Number 2021YFF0501400 and Key project of National Natural Science Foundation of China under Award Number 81930044.JA was employed by Siemens Shenzhen Magnetic Resonance Ltd. 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.


Non-responders to Cardiac Resynchronization Therapy (CRT) represent a high-risk, and difficult to treat population of heart failure patients. Studies have shown that these patients have a lower quality of life and reduced life expectancy compared to those who respond to CRT. Whilst the first-line treatment for dyssynchronous heart failure is “conventional” biventricular epicardial CRT, a range of novel pacing interventions have emerged as potential alternatives. This has raised the question whether these new treatments may be useful as a second-line pacing intervention for treating non-responders, or indeed, whether some patients may benefit from these as a first-line option. In this review, we will examine the current evidence for four pacing interventions in the context of treatment of conventional CRT non-responders: CRT optimization; multisite left ventricular pacing; left ventricular endocardial pacing and conduction system pacing. Cardiac Resynchronization Therapy (CRT), in addition to optimal medical therapy, is a widespread and successful treatment for patients with dyssynchronous heart failure (HF) . ConventUnfortunately, there is a subgroup of high-risk patients who have a poor therapeutic response to CRT, so-called “CRT non-responders” representing between 30% and 50% of CRT patients . SeveralTreatment of CRT non-responders is extremely difficult, and this cohort of patients is known to have poor outcomes . In receIn this review, we will examine the current data for these four pacing interventions in the treatment of CRT non-responders, discuss the limitations of the current body of evidence, and provide opinions on future directions in this field.Delay optimisation has been the subject of investigation since the advent of CRT, arising from the theory that optimisation of both passive and active filling will maximise cardiac output, thereby improving outcomes. Observational studies have reported acute haemodynamic and electrical benefits of AV/VV optimisation in patients receiving CRT , howeverThere are several reasons why acute mechanistic data examining haemodynamic benefits of AV delay optimisation do not translate to improve outcomes in clinical trials. The intrinsic PR interval is variable, especially in response to factors such as autonomic tone and exercise . As suchp < .001) and LV end-systolic volume from 108.5 ± 37.6 to 98.0 ± 37.5 mL (p = .009). Additionally, speckle-tracking measures of LV strain significantly improved by 2.4% ± 4.5%  and 1.0% ± 2.6%  and aortic to pulmonic valve opening time, a measure of interventricular dyssynchrony, significantly (p = .040) decreased by 14.9 ± 39.4 ms  and multi-lead pacing, such as “triventricular” (TriV) pacing is a well-studied area in the field of CRT non-response. Pacing the LV from multiple locations is an attractive concept as it potentially addresses the problems caused by ischaemic scar or other areas of slow conduction velocity that reduce the efficacy of CRT by affecting the LV paced wavefront. Several studies testing the efficacy of these interventions have been performed in non-responder populations. In the SMART-MSP trial, 102 patients who had an unchanged or worsened clinical composite score,  at 6 months post-CRT had LV MPP turned on . They foMulti-lead pacing, that is, the placement of an additional lead, most commonly in the LV to provide Triventricular (TriV) pacing , has alsAcute haemodynamic studies in both animals  and humap = 0.014) and resulted in a shorter paced QRS duration . Interestingly, Sohal et al. , or a leadless pacemaker such as MICRA™ . The transmitter and battery detect an RV pacing pulse emitted by the co-implant. Within 10 ms of detection of the RV pacing spike, the transmitter emits a number of ultrasound pulses to locate the receiver electrode. Once the transmitter is electronically optimally aligned, a longer ultrasound wave is emitted, which is detected and converted to a pacing stimulus by the receiver electrode. This results in LV pacing, and thereby BiV pacing.The WiSE-CRT system  is the only commercially available leadless LV pacing system . The sysp < 0.001, with low heterogeneity . The echocardiographic response rate  was 54% in a population where 22% were non-responders to conventional CRT.Several observational studies have demonstrated that treatment with WiSE-CRT can deliver echocardiographic CRT response . A recenp = .002) and improvement in left ventricular ejection fraction (LVEF) . Overall, 55.6% of patients had improvement in their clinical composite score  and 66.7% had a reduction in LVESV ≥15% and/or absolute improvement in LVEF ≥5%. These results, albeit in a small patient cohort, provide preliminary favourable feasibility data of WiSE-CRT in treatment of non-responders. The ongoing SOLVE-CRT trial (NCT02922036)  , a multiin silico studies and observational studies.Conduction system pacing (CSP) is an area of rapidly growing interest, built upon the attractive concept of restoring completely physiological ventricular activation. Initial studies in lead-based CSP focused on His Bundle Pacing (HBP). HBP achieves excellent cardiac resynchronization, but implantation can be difficult with success rates varying from 56%–95% . Concernin silico study examining ventricular activation times on 24 four chamber heart meshes in the presence of simulated left bundle branch block (LBBB). They simulated BiV epicardial and BiV endocardial pacing, as well as HBP and LBBAP. They reported that HBP was superior (p < .05) to BiV endocardial and conventional BiV pacing with regards to reduction in LV activation time (AT) and interventricular dyssynchrony, , or CRT non-response  (p = .007). The incidence of clinical and echocardiographic improvements in Group 1 was similar to those observed in patients undergoing conventional CRT in clinical trials. The authors concluded that LBBAP is a reasonable alternative to BiV CRT but more work is needed to assess its efficacy in non-responders.Data from observational trials comparing conventional CRT with CSP in both unselected patients and non-responders has had variable outcomes. Non-randomised observational studies by Chen et al. and Vijayaraman et al.  demonstrplicated . Interes n = 44) . QRS durp = 0.003), to 151 ± 24 ms during HBP (p < 0.0001), and further to 120 ± 16 ms during HOT-CRT (p < 0.0001). During a mean follow-up of 14 ± 10 months, LV ejection fraction improved from 24 ± 7% to 38 ± 10% (p < 0.0001), and NYHA functional class changed from 3.3 to 2.04. Twenty-one of 25 patients (84%) were clinical responders while 23 of 25 (92%) demonstrated an echocardiographic response. A LOT-CRT feasibility study  or LBP-Optimised CRT (LOT-CRT). A mechanistic study of 11 patients showed that pressure-volume derived stroke volume was optimal when LV pacing was combined with HBP, suggesting that sequential CSP-LV activation provides benefit by preserving intrinsic RV activation . A 25 paty study  reportedty study . This isty study , extractty study .p = .009). One of these 8 patients was a CRT non-responder, with the remainder being transvenous LV epicardial lead failures. Further data in this regard will come with time-LV septal implants are projected to increase in view of an improved safety profile of trans-septal compared to large-bore aortic access, and historically, around 1 in 5 patients receiving WiSE-CRT have been conventional CRT non-responders  of greater than 15% being the most useful measure . HoweverUltimately, determining the optimal second-line pacing intervention in CRT will require well designed clinical trials examining a standardised population of patients, with strict non-response inclusion criteria. Whilst early studies including WiSE-CRT , HOT-CRTIn summary, the heterogeneity of the dyssynchronous HF population and the high success rates of empirical conventional CRT mean that generating robust evidence for the optimal pacing alternatives for CRT non-responders is extremely challenging. There is likely a significant subgroup of CRT non-responders who have a superior alternative pacing location, in particular those who have problems with conventional LV lead implantation, or poor LV lead performance due to issues such as high capture thresholds and phrenic nerve stimulation. The plethora of novel therapies including endocardial and conduction system pacing may enable physicians to deliver tailored CRT for individual patients. Further study concentrating on patient selection will ultimately pave the way for this form of precision medicine.


Arterial hypertension, especially when coexisting with other cardiovascular risk factors, could determine an imbalance between myocardial energetic demand and altered efficiency, leading to an early left ventricular (LV) systolic dysfunction, even in terms of echo-derived mechano-energetic efficiency indexed for myocardial mass (MEEi). We aim to analyse an improvement in LV MEEi, if any, in a population of hypertensive patients with a long-term follow-up and to identify clinical, metabolic and therapeutic determinants of LV MEEi amelioration.In total, 7,052 hypertensive patients, followed-up for 5.3 ± 4.5 years, enrolled in the Campania Salute Network, underwent echocardiographic and clinical evaluation. LV MEEi was obtained as the ratio between stroke volume and heart rate and normalized per grams of LV mass and ΔMEEi was calculated as difference between follow-up and baseline MEEi. Patients in the highest ΔMEEi quartile (≥0.0454 mL/s/g) (group 1) were compared to the merged first, second and third quartiles (<0.0454 mL/s/g) (group 2). METS-IR (Metabolic Score for Insulin Resistance), an established index of insulin sensitivity, was also derived.p = 0.02). After excluding patients experiencing cardiovascular events, patients in group 1 were younger (p < 0.0001), less often diabetic (p = 0.001) and obese (p = 0.035). Group 1 experienced more frequently LV mass index reduction, lower occurrence of LV ejection fraction reduction, and had a better metabolic control in terms of mean METS-IR during the follow-up . Beta-blockers were more often used in group 1 (p < 0.0001) than group 2. A logistic regression analysis showed that younger age, lower mean METS-IR values, more frequent LV mass index reduction and therapy with beta-blockers were significantly associated with LV MEEi improvement, independently of presence of diabetes and obesity.Patients with MEEi improvement experienced a lower rate of major cardiovascular events (Metabolic control and therapy with beta-blockers could act in a synergic way, determining an improvement in LV MEEi in hypertensive patients over time, possibly confining cardiac damage and hampering progression toward heart failure. Arterial hypertension, in particular when associated with additional cardiovascular risk factors, induces an imbalance in cardiac metabolism by increasing myocardial energetic demand and impairing energetic efficiency. This condition represents an early cardiac damage, which increases the risk of progression toward heart failure –4.Ultrasound assessment represents an accurate and wide available methodology to identify this early left ventricular (LV) functional impairment in the hypertensive setting . Indeed,On the other hand, it is still unclear whether the control of risk factors by modification of life habits and diet and effective therapeutic strategies can improve an impaired MEEi in hypertensive patients. Indeed, it has been demonstrated that both effective antihypertensive therapy and weight loss could induce a positive remodeling of the left ventricle over time, with a regression of LV mass and amelioration of LV systolic function –13. In aThus, we assessed the time-course of MEEi in a population of hypertensive patients with a long-term follow up, to test the possibility to improve an impaired LV MEEi and to identify clinical, metabolic, even in terms of METS-IR, and pharmacological determinants of such an increase in MEEi, if any, and its relevance on cardiovascular prognosis.ClinicalTrials.gov Identifier: NCT02211365)  . All pat2211365) .Inclusion criteria were: (1) age more than 18 years; (2) available follow-up with echo assessment ≥ 12 months; (3) no history of prevalent cardiovascular disease, including myocardial infarction, angina pectoris, coronary or carotid revascularization procedures, stroke, transitory ischemic attack, congestive heart failure, clinically relevant heart valvular disease , chronic kidney disease more than stage 3; (4)available baseline echocardiographic and carotid ultrasound assessment; 4) LVEF > 50% at baseline echocardiographic exam; (5) ability to give informed consent.The rate of major cardiovascular events, that happened during the follow-up period, was related to the first occurrence. Major cardiovascular events developed during the follow-up included myocardial infarction, coronary or carotid revascularization procedures, stroke and transitory ischemic attack.Diagnosis of arterial hypertension was established on the basis of current ESC/ESH guidelines . Heart rGlomerular filtration rate was measured with the chronic kidney disease epidemiology collaboration (CKD-EPI) equation .2. Weight loss was described as a reduction in body weight ≥ 5% at the final available visit, compared to initial value, as previously reported /ln [HDL-Cholesterol (mg/dL)]}  + Triglycerides (mg/dL)] × Body Mass Index (kg/mmg/dL)]} .All echocardiographic exams were performed at the Hypertension Outpatient Clinic of the Federico II University in Naples, using a standardized protocol. All measurements were evaluated according to the latest consolidated convention , 23.2.7 in women and >50 g/m2.7 in men  , 25. LV 7 in men , 27. LV reported .Left ventricular ejection fraction and stroke volume were computed as the difference between LV end- diastolic and end-systolic volume by the z-derived method and indexed for height to the power of 2.04 , 29. LVELeft ventricular myocardial mechano-energetic efficiency was computed as the ratio between stroke volume and heart rate and normalized per grams of LV mass, and expressed in mL/s/g (MEEi), as previously reported . Delta MLeft atrial volume was estimated according to previously validated formula and indexed for height powered to 2 .Carotid ultrasound was assessed in supine position. The intima–media thickness was measured as the distance between lumen-intima and media-adventitia interface in up to 2 arterial walls, on both near and far walls of distal common carotid (1 cm), bifurcation and proximal internal carotid artery of both sides and carotid plaques were defined for intima–media thickness values > 1.5 mm .t-test were used to test differences in dichotomous/categorical and continuous covariates, respectively.Categorical variables were expressed as number (percentage) and continuous variables as mean ± standard deviation or median [interquartile range] when not normally distributed. Chi-square test and Student’s Delta MEEi quartiles were computed: first quartile for delta MEEi ≤ −0.0354 mL/s/g, second quartile ranging from −0.0354 to ≤0.0028 mL/s/g, third quartile from 0.0028 to <0.0454 mL/s/g, fourth (highest) quartile ≥ 0.0454 mL/s/g. The study population was divided into two groups: patients who presented an improvement in MEEi as highest delta MEEI quartile (group 1), were compared to patients of the merged first, second and third delta MEEi quartiles (group 2). Univariate logistic regression analyses were assessed to verify important variables for delta MEEi improvement.A logistic regression model was built including the significant variables derived from univariate correlations in order to identify possible factors associated with LV MEEi improvement in terms of highest delta MEEi quartile. Calculation of tolerance and variance inflation was performed by linear modeling and collinearity was considered acceptable for variance inflation factor less than 3.p-value < 0.05 was considered statistically significant. All statistical analyses were performed using SPSS Statistics 26 software .In all analyses a p = 0.02).Patients were followed-up for 5.3 ± 4.5 years and during this period major cardiovascular events occurred in 165 patients with a prevalence of 1.5% among those showing an improvement of MEEi which was significantly lower when compared with the one of patients who did not experience any increase or even a decrease in MEEi  mmHg vs. −5 (−15 to 2) mmHg, p < 0.0001]. In addition, patients in group 1 had a higher prevalence of LV mass index reduction and a better metabolic control in terms of METS-IR, lower mean serum triglycerides, mean fasting glucose plasma levels and higher mean HDL cholesterol levels, while lower BMI (body mass index) values during the follow-up (p < 0.0001).Despite patients of group 1 and group 2 reached comparable BP values during the follow-up, patients in group 1 experienced a larger reduction in BP values since they had higher BP values at baseline; indeed, patients of group 1 presented a higher delta reduction in both systolic BP and diastolic BP from baseline to the end of the follow-up than group 2, [median (interquartile range)] [delta systolic BP = −8 (−22 to 5) mmHg vs. −5 (−20 to 8) mmHg, ollow-up . FurtherRegarding treatment, beta blockers were more often used in group 1, whereas antiplatelet therapy and dihydropyridine Calcium channel blockers were more often used in group 2.Univariate logistic regressions showed that age, diabetes mellitus, obesity, mean fasting plasma glucose, mean triglycerides, mean HDL cholesterol levels during the follow up, mean METS-IR, LV mass index reduction, therapy with dihydropyridine Calcium channel blockers, antiplatelet therapy and therapy with beta-blockers present in more than 50% of the follow-up were significantly related to delta LV MEEi improvement .A logistic regression analysis  showed tThe current study demonstrated that: (1) an improvement in MEEi in hypertensive patients is achievable; (2) during the follow up the largest MEEi improvement was associated with a significantly lower prevalence of major cardiovascular events; (3) after excluding patients who experienced major cardiovascular events, those with the largest improvement in MEEi were the ones who had the lower rate of reduction in LVEF during the follow-up, (4) better metabolic control, in terms of METS-IR, and higher rate of LV mass reduction were directly associated to LV MEEi improvement during the follow-up, independently of the presence of diabetes and obesity, (5) among treatments, therapy with beta-blockers was significantly and independently associated with LV MEEi improvement.The possibility to identify the determinants of an amelioration in LV mechanic-efficiency could be of relevant interest, since the recognition of the factors and therapies contributing to preserve LV performance could avoid the progression of cardiac impairment demonstrated to be associated with arterial hypertension, especially when in combination with additional cardiovascular risk factors , 35. TheLow MEEi values, indeed, were showed to be a reliable predictor of cardiovascular events and heart failure and values below 0.29 of this index were demonstrated to be associated with systolic dysfunction and LVEF reduction .On this basis, in the present study we investigated the possibility of an improvement of LV MEEi in terms of delta MEEi from baseline to the end of a long-term follow-up in a population of hypertensive patients, its clinical relevance and its determinants.We confirmed that an improvement in MEEi is possible and that it is clinically relevant since patients in the highest delta MEEi quartile experienced a lower rate of cardiovascular events during the follow-up.Furthermore, in order to exclude the confounding factor related to a reduction of MEEi in the occurrence of major cardiovascular events during the follow-up, we excluded those patients from subsequent analysis.Left ventricular MEEi improvement of the highest delta quartile (≥0.0454 mL/s/g) means that patients possibly jumped from the lowest quartile of MEEi at baseline to the third or to the highest quartile at the end of the follow-up. In the present study, we observed that patients who experienced an improvement of LV MEEi had at baseline higher BP and heart rate values, they were younger, less often diabetic and obese and had better lipidic and glucose serum profile together with better renal function. At baseline they seem to have a slightly but significant impairment in both LV morphology  and function (lower LV EF and stroke volume). Mean blood pressure and heart rate values were comparable during the follow-up, meaning that patients in the highest delta MEEi quartile achieved a more pronounced decrease in BP values and heart rate, since they had significantly higher values at baseline. In addition, during the follow-up they maintained a better metabolic control with lower values of serum fasting plasma glucose, triglycerides, lower body weight and BMI, and higher serum HDL-cholesterol. This also resulted in lower values of METS-IR. The latter was demonstrated to be an established index for the evaluation of insulin sensitivity and of cardiovascular risk, containing in its computation information about fasting plasma glucose, serum triglycerides, HDL-cholesterol levels and BMI . FurtherA logistic regression analysis provided additional information. After adjusting for age, mean METS-IR, prevalence of diabetes and obesity, LV mass index reduction, use of beta-blockers, dihydropyridine Calcium channel blockers and antiplatelet therapy, the improvement in MEEi from baseline to the end of the follow-up was significantly associated with younger age, better metabolic control in terms of METS-IR, more frequent LV mass index reduction and therapy with beta blockers, independently of the presence of diabetes and obesity, whereas therapy with dihydropyridine Calcium channel blockers was negatively associated with MEEi improvement.These findings corroborate previous observations demonstrating the beneficial impact of the reduction of both body weight and BMI and insulin resistance on LV morphology and function and extend them in a population of hypertensive patients with several additional cardiovascular risk factors and a long-term follow-up , 12. IndAmong therapeutic approaches only beta-blockers resulted to have a beneficial effect on LV MEEi improvement. Current guidelines for the management of arterial hypertension suggests the use of combination therapies based on renin-angiotensin-aldosterone system inhibitors, diuretics and dihydropyridine calcium-channel blockers for most of hypertensive patients . NonetheFurthermore, it is possible to speculate that the negative association of dihydropyridine calcium channel blockers with the highest delta LV MEEi quartile may be related to the increase in sympathetic discharge that these drugs induce through a baroreceptor reflex, which leads to an increase in heart rate, negatively impacting on MEEi .Thus, both metabolic control and beta-blockers, acting in a synergic way, had a favorable effect on LV function and morphology inducing an improvement in cardiovascular prognosis detectable by the increase in LV MEEi.Additional sensitive parameters for the evaluation of LV systolic function, such as global longitudinal strain and strain derived myocardial work components, are missing in the present study. Nevertheless, MEEi is a sensitive and well-established parameter of LV systolic performance and has the advantage of being derived from standard echocardiographic assessment without the need of additional software. Moreover, information about which type of antidiabetic therapy was administered in the study population is missing, together with info about serum glycated hemoglobin values. Nonetheless, in the present study we demonstrated that metabolic control in terms of METS-IR was a significant determinant of LV MEEi improvement independently of the presence of diabetes. Furthermore, the Campania Salute Network is an observational registry, and it could possibly be influenced by selection bias. However, all patients underwent the same visits and echocardiographic evaluations and followed the same standardized protocol.In a population of hypertensive patients with several cardiovascular risk factors, metabolic control and therapy with beta-blockers were significantly associated with an improvement in LV systolic performance in terms of LV MEEi during a long-term follow-up, thus corroborating the usefulness of this parameter, easily obtainable from standard echocardiographic assessment. LV MEEi improvement was independent of the presence of diabetes and obesity and clinically relevant, as demonstrated by a lower prevalence of major cardiovascular events and occurrence of LVEF reduction. All together our results demonstrate the importance of early obtaining and maintaining adequate metabolic profile and insulin sensitivity in hypertensive patients in order to possibly limit myocardial damage and progression toward heart failure.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Federico II University Hospital Ethical Committee. The patients/participants provided their written informed consent to participate in this study.ML wrote the manuscript. VT helped in writing the manuscript and data collection. MM and CMa collect the clinical and echo data and performed the statistical analysis. GE, SE, and CMo critically revised the manuscript. RI and BT conceived the idea and critically revised the manuscript. All authors give final approval to the submission of the manuscript.


Ischemic Myocardial Injury and Protection: From Bench to Bedside” for the readers of Frontiers in Cardiovascular Medicine. This Research Topic includes twelves article and one review gathering an interdisciplinary overview of molecular mechanism, high risk factor, prognosis, complication, and novel treatment of ischemic myocardial injury.Ischemic heart disease (IHD) remains the primary cause of global mortality , and has been considered as a life-threatening problem –4. AlthoQi et al. found blockade of NaV1.8 in cardiac ganglionated plexi (GP) increased the incidence of ventricular arrhythmias in acute myocardial infarction (AMI) hearts. Present results indicated suppression of GP activity might enhance the genesis of ventricular arrhythmia; NaV1.8 plays an important role in cardiac conduction via regulation of action potential firing in intracardiac neurons. Qi et al. observed that NaV1.8 was expressed in canine GPs, blockade of NaV1.8 with A-803467 shortened ventricular effective refractory period (VERP), ventricular 90% of action potential duration (APD90), and decreased ventricular fibrillation threshold (VFT) during AMI, and also reduced heart rate in response to GP stimulation. Although the detailed mechanisms are needed to further study to clarify, the study suggests NaV1.8 may be as a potential novel therapeutic target for anti-arrhythmic intervention and prevention of SCD of patients with IHD.The high mortality of IHD is attributed to sudden cardiac death (SCD), which results from lethal ventricular arrhythmias of ventricular tachycardia (VT) . Qi et aLi, Zhao et al. demonstrated plasma exosomes at the late phase of remote ischemic pre-conditioning (RIPC) alleviated myocardial ischemia-reperfusion injury via exosomal miR-126a-3p. On the basis of cardiac-protection of exosomes at the late phase of RIPC, they found the significant enrichment of miR-126a-3p in RIPC-exosome by miRNA array. Mechanistically, RIPC-exosomal miR-126a-3p, activated reperfusion injury salvage kinase (RISK) through Akt and Erk1/2 to inhibit apoptosis. This study is interesting, and presents a critical mechanism underlying the exosomal miR-126a-3p might be a novel cardioprotective molecule in the prevention and rehabilitation of ischemic myocardial injury. However, Tu et al. showed that sepsis-exosomes promoted the pyroptosis of cardiomyocytes and worsened cardiac dysfunction through miR-885-5p via HMBOX1. These findings suggest the different mechanisms or functions of exosomes in ischemic myocardial injury may dependent on exosomal source of pathophysiological process or cell-types.Exosomes derived from a variety of cardiac cells have been reported to regulate intercellular communication and crosstalk in ischemic heart by the transfer of miRNA or other proteins . Li, ZhaLiu et al. verified that downregulation of rno_circRNA_0009197, and upregulation of rno_circRNA_0005304, rno_circRNA_0005506, rno_circRNA_0005818, and rno_circRNA_0009301 in hypertensive aorta. Three promising circRNA-miRNA-mRNA regulatory axes, including rno_circRNA_0005818/miR-615/NOTCH1, rno_circRNA_0005818/miR-10b-5p/STAT3, and rrno_circRNA_0009197/miR-509-5p/FOXO3, may play potential roles in hypertensive vascular remodeling and dysfunction. The findings indicate that circRNAs are the vital therapeutic targets for ischemic heart diseases and vascular diseases.Circular RNAs (circRNAs), function as a sponge and bind specific miRNAs to exert critical effects in ischemic heart diseases and vascular diseases. 2S), an endogenously generated gaseous transmitter, has been shown to be cardiac protective in ischemic myocardial injury or heart failure , a novel modulator of endogenous H2S. SPRC has been identified to be protective in myocardial infarction via a H2S-related pathway , LV diastolic dysfunction, arteriosclerosis, and microalbuminuria. Yu et al. performed a single-center, observational cohort study enrolled 183 acute heart failure (AHF) patients and evaluate the association between the serum circulating free fatty acids (FFAs) level and all-cause mortality or HF rehospitalization. Serum FFAs levels were positively correlated to the risk of death or HF rehospitalization, which was not related to the status of insulin resistance. In this retrospective cross-sectional study, patients who underwent elective percutaneous coronary intervention (PCI). Li, Li et al. found elevated HbA1c increased the atherosclerotic plaque vulnerability as evidenced by the thinner minimal fibrous cap thickness (FCT), higher lipid index, and greater macrophage index. Moreover, elevated average follow-up HbA1c level was positively associated with higher visit-to-visit variability of lipids levels, including LDL-C, HDL-C, non-HDL-C, TC, and TG. Our basic research showed deficiency of cardiac LRP6 induced lipid accumulation and heart failure, and overexpression of low-density lipoprotein receptor-related protein 6 (LRP6) protects heart from ischemic-reperfusion injury in mice  or IHD. Metabolic syndrome (MS) is characterized by a cluster of risk factors including central obesity hypertension, hyperglycemia, and dyslipidemia, significantly increases the risk for cardiovascular disease (CVD), or the morbidity and mortality of CVD patients . Zhao F. in mice –13. ThesMo et al. identified three novel predictors for CIN, baseline uric acid level, creatine kinase-MB level, and log  level, in patients with CAD and relatively normal renal function (NRF). The authors developed the simplified risk score for contrast induced acute kidney injury (CI-AKI) model on the basis of the new criteria. It exhibits accurate predictive performance to identify high-risk patients with CIN. For drug treatment, β-blockers predominantly increase sympathetic nerve activity, and become the first-line agent for cardiovascular diseases. However, Dai et al. found β-blockers adversely affected erectile dysfunction (ED) improvement conferred by coronary revascularization in patients with early onset of coronary artery disease (EOCAD). This study calls for re-considering β-blockers as the first-line option for the EOCAD patients with ED.In treatment of CAD or IHD, PCI has become one of most effective treatments for patients with AMI. But it also induces some complications in patients such as contrast induced nephropathy (CIN), caused by intravascular contrast media. Zhao Y. et al. systemically reviewed the types, the beneficial effects and molecular mechanisms of ES in the treatment of IHD. ES promotes angiogenesis by stimulating VEGF or FGF2 secretion, reduces cardiomyocytes apoptosis by inhibiting the production of TNF-α and intercellular adhesion factor-1 (ICAM-1), inhibits cardiac hypertrophy by suppression of ERK1/2 signaling, in the ischemic myocardium. ES also protects heart from ischemic injury by regulation of autophagy, inflammatory response and the production of ROS. This exhaustive review prompts to investigate in depth the molecular mechanisms underlying ES to develop new therapeutic opportunities. The authors suggest that appropriate parameters and implementation methods and locations of ES are needed further study to provide better scientific data for clinical application in IHD. Moreover, cardiac shock wave therapy (CSWT), has been reported to be an effective and non-invasive therapy, which is mainly applied to ameliorate left ventricular remodeling after (AMI). Wang et al. found the application of CSWT significantly improved cardiac function and myocardial fibrosis by activation of PI3k /AKT signaling in experimental AMI model. Moreover, renal denervation (RDN) reduces the activation of the sympathetic nervous system (SNS) and renin-angiotensin-aldosterone system (RAAS) for hypertension treatment. Chen et al. investigated the cardioprotective effects of immediate renal denervation (RDN) after AMI and explored the underlying mechanism. They found immediate RDN could improve cardiac remodeling and function after AMI via regulation of IL-33/ST2 and downstream signaling. The study suggests RDN may become another viable application in emergency PCI beyond hypertension.Some researchers explored novel intervention for ischemic myocardial injury. Electrical stimulation (ES), a non-invasive and safe physiotherapy, is considered to be a promising clinical application in the treatment of IHD, which attracts more and more attention. In conclusion, the articles collected for this Research Topic present current progress and perspectives on the pre-clinical, clinical and epidemiological studies on the ischemic myocardial injury and protection. We believe that these articles advance our understanding and perspectives on cardiovascular diseases fields. We are grateful for all contributors for sharing their interesting work for the Research Topic.HG wrote the manuscript. HT and YT revised the manuscript. All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.This work was supported by grants from National Natural Science Foundation of China (NSFC)  and Science and Technology Commission of Shanghai Municipality (21XD1403300 for HG).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.


Acute coronary syndrome (ACS) is a group of clinical syndromes caused by acute myocardial ischemia, mainly including ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), and unstable angina. It is commonly attributed to the rupture of atherosclerotic plaques and secondary acute intracoronary thrombosis, and patients may die from acute myocardial ischemia after experiencing chest discomfort and dyspnea . Each yeSelected papers in this research theme discuss recent advances in multi-modality imaging (MMI) of ACS including both non-invasive and invasive techniques, which provide great insight into the etiology and pathology of ACS, and also demonstrate application of new technologies to refine the existing diagnostic system for ACS.Lin et al. reported the enhanced effect of global myocardial work efficiency (GWE) as a novel parameter of left ventricular function measurement, affirming the improved diagnostic ability of GWE in combination with myocardial layer-specific strain for CAD.As the preferred screening tool for patients with suspected coronary artery disease (CAD), stress echocardiography can increase diagnostic efficacy and reduce medically induced injury but still with unsatisfactory specificity and sensitivity . Lin et Bae et al. described how the sum of the abnormal diastolic function markers was measured by transthoracic echocardiography, from which the left ventricular wall motion score index (WMSI) was calculated. They emphasized the application of this comprehensive scoring method for long-term prognosis and risk stratification of CAD.Left ventricular systolic and diastolic dysfunction suggests possible structural myocardial injury, and the predictive role of a single left ventricular diastolic function (LVDF) marker for the occurrence of adverse events in patients with post-acute myocardial ischemia (AMI) is well-established. Ling et al. provided comprehensive assessment of coronary structure and function in the above population. With the add-on of late iodine enhancement (LIE) for myocardial scar identification, dynamic computed tomography myocardial perfusion imaging (CT-MPI) combined with coronary computed tomographic angiography (CCTA) is not only equivalent to CMR in etiologic assessment, but also provides additional visualization of coronary artery wall and luminal structures to guide clinical intervention and prognostic management of patients with ACS. CCTA assessment of functional coronary stenosis is challenging and requires myocardial blood flow (MBF) as a complement to physiological information, which is generally obtained by positron emission tomography (PET) and magnetic resonance imaging (MRI). However, CT-MPI, also as a MBF assessment tool, has limited use in clinical practice. The study by Lyu et al. obtained MBF cut-off values for dynamic CT-MPI which can differentiate healthy subjects from patients with functional myocardial ischemia, establishing the basis for the development of future universal datasets.Approximately 6% of AMI patients do not exhibit acute coronary obstruction . There aMatsuda et al. demonstrated the ability of CCTA to detect non-infarct-related UMI before invasive coronary angiography.Unrecognized myocardial infarction (UMI) accounts for approximately more than 50% of all myocardial infarctions and is difficult to recognize due to its asymptomatic syndromes . In thisLuo et al. validated the ability of serum soluble suppression of tumorigenicity-2 (sST2) to predict plaque tissue composition in patients with NSTEMI using standard CCTA and coronary angiography. Assessment of coronary lesions by inflammatory factors combined with imaging techniques may be one of the key future directions.Intravascular ultrasound (IVUS) or optical coherence tomography (OCT) enables high resolution imaging of atherosclerotic plaques but is limited by its invasive nature. With the rapid development of non-invasive imaging technologies, it would be interesting to see whether non-invasive methods can approach the diagnostic accuracy of invasive methods for plaque characterization. Lu et al. CCTA stood out when clinicians need an “one-stop shop” examination to assess coronary anatomy, histological features of atherosclerotic plaques and hemodynamics. It can comprehensively evaluate the condition of almost all coronary arteries and branches macroscopically, while identifying the characteristics of high-risk atherosclerotic plaques with high precision. The authors discussed the application of CCTA in predicting the occurrence of ACS and patient risk assessment, and provided an overview of some emerging techniques such as computational fluid dynamics.The diagnostic value of CCTA on unstable plaques and surrounding environment was likewise confirmed by Zhang et al. enumerated the diagnostic performance of different types of CT techniques in the assessment of vascular calcification including coronary calcification. Multi-slice spiral CT and dual-energy CT are commonly used in clinical practice to detect and quantify the extent of arterial calcification and assess high-risk plaque features. Emerging CT techniques including multi-slice spinal CT, micro CT, ultra-high resolution CT and etc., aim to enhance the detection of microcalcification by improving the imaging resolution.The predictive function of coronary calcification on cardiovascular morbidity and mortality has been confirmed by previous studies and CT is considered the gold standard. Alasnag et al. established the ACS cardiac computed tomography (CCT) protocol and treatment strategy, and validated the role of CCT in the evaluation of low risk ACS. Although this study is only a single-center trial, it has demonstrated the role of CCT in the anatomical risk stratification and has encouraged us to take on new challenges in special settings when working with conventional imaging.The Coronavirus Disease 2019 (COVID 19) pandemic challenges traditional ACS assessment pathways, and it is sometimes of high demand to limit the spread of infection by avoiding unnecessary invasive procedures and curtailing the length of patient stay. Based on the GRACE Score, hemodynamics, and patients' COVID19 status, in vivo, CMR can be used for risk stratification and prognostic management of patients with STEMI  assessment and myocardial enhancement.As LGE has become an established technique for marking infarcted myocardium th STEMI , 8. SubtCalvieri et al. demonstrated the role of CMR in assessing the efficacy of cardioprotective therapies. CMR feature tracking analysis (CMR-FT), which is able to quantitatively assess subtle deformation in response to myocardial motion, detected adverse ventricular remodeling at an early stage.Left ventricular remodeling after STEMI is associated with adverse cardiovascular events in patients, and current guidelines recommend that patients improve their prognosis by taking aspirin prior to percutaneous coronary intervention (PCI) , 9. CalvLai et al. affirmed the established role of CMR myocardial strain measurements for adverse events and the prognostic significance of the combined assessment of both left and right ventricular strain indexes.Impairment of LV strain predicts possible subsequent ventricular remodeling and worsening ejection fraction, raising concerns among clinicians. With the development of new therapies, short-term mortality in patients with STEMI has decreased substantially, however, long-term prognosis varies widely. Accurate and clinical available indicators for risk stratification are able to aid in the early identification of high-risk patients. Qi et al. reviewed the progress of commonly used imaging methods in detecting coronary microvascular angina. Both single-photon emission computed tomography (SPECT) and PET-MPI quantify myocardial blood flow, with the latter being more sensitive and specific. CMR is sensitive to early lesions and allows qualitative and quantitative visualization of coronary microcirculation. Myocardial contrast echocardiography is commonly used for preliminary screening and in recent years has also been developed for therapeutic purposes. CT allows for a comprehensive assessment of non-coronary ischemic heart disease (INOCA).Complications of diabetes often involve the microcirculatory system, and patients can develop angina secondary to microcirculatory dysfunction. Kubo et al. evaluated the combined use of multiple intravascular imaging techniques in ACS with their respective strengths and weaknesses. Both IVUS and OCT provide cross-sectional images of coronary arteries. IVUS provides better penetration, and can assess the size of both the lumen and external elastic lamina of the vessel, and therefore is valuable for assessing plaque burden. OCT has higher resolution but shallower penetration depth, and can detect thin cap fibroatheroma, also known as vulnerable plaque  in patients with STEMI, providing evidence for future establishment of a personalized treatment system. They focused on patients with poorer prognosis for non-infarct-related arterial disease (NIRA), who may require a more aggressive treatment approach.Several studies have shown that there are anatomical, pathological and clinical differences between male and female CAD patients, and using the same cardiovascular assessment criteria does not provide appropriate treatment recommendations and prognostic assessments. Liu C. et al. demonstrated that immunoinflammatory biomarkers such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were associated with a high risk of QFR ≤ 0.8. It is suggested that combining inflammatory markers with imaging parameters can significantly improve the identification of functional severe CAD by predicting functional ischemia and anatomic stenosis.Previous studies have shown that both the immune system and inflammatory cells promote plaque progression and aggravate coronary artery stenosis , 13. LiuWang et al. found that coronary physiology and deceleration capacity (DC) combined with QFR were able to improve the predictive accuracy of major adverse cardiac and cerebrovascular events.PCI is the one of the routine treatments for STEMI, but approximately 20% patients who fail functional revascularization still experience adverse coronary events after the procedure. FFR can predict patient prognosis by evaluating functional stenosis of the coronary arteries. Liu M-h. et al. discussed the advantages of AI combined with MMI in filling the gaps of ACS management strategies. With massive data collection and powerful processing capabilities, AI, in particular deep learning, learns and exacts hierarchal features from clinical data automatically and is valuable for lesion identification and segmentation, disease classification, clinical recommendation, and prognosis prediction. With the help of AI, diagnostic performance can be significantly improved ranging from non-invasive imaging techniques such as CT and CMR to invasive imaging techniques such as coronary angiography (CAG), OCT and IVUS.The comprehensive assessment of ACS often involves multiple imaging modalities, demanding real-time, objective and precise diagnosis. It's thrilling to see the fast pace multimodality imaging technologies have been developed in the evaluation of ACS for the past decade. In addition, the advances of new technologies can further help physicians and bring benefits to patients. The combination of multiple imaging modalities, the addition of AI technology and the joint application of biological markers and imaging techniques have already evolved into mainstream directions for future research, which may bring fundamental changes to the diagnosis and management of ACS.YW wrote the first draft of the manuscript. ZW, JT, and ML wrote sections of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.This work was supported by the Construction Research Project of the Key Laboratory (Cultivation) of Chinese Academy of Medical Sciences (2019PT310025), National Natural Science Foundation of China (81971588), Youth Key Program of High-level Hospital Clinical Research (2022-GSP-QZ-5), the Applied Technology Research and Development Plan of Heilongjiang Province (GY2020YF0039 to JT) and the Fok Ying-Tong Education Foundation for Young Teachers (171032 to JT).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. 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To assess the recovery and prognostic values of myocardial strain using cardiac magnetic resonance (CMR)- feature tracking (FT) in acute anterior and non-anterior wall myocardial infarction.103 reperfused patients after STEMI who underwent CMR at about 4 days (baseline) and 4 months (follow-up) were included, including 48 and 55 patients with anterior wall myocardial infarction (AWMI) and non-anterior wall myocardial infarction(NAWMI). CMR-FT analysis was performed using cine images to measure LV global radial, circumferential, and longitudinal peak strains . Infarct size (IS) and microvascular obstruction (MVO) were estimated by late-gadolinium enhancement imaging. The primary clinical endpoint was the occurrence of major adverse cardiac events (MACE) after infarction.Patients with AWMI had higher IS, higher MVO, lower ejection fraction, and more significantly impaired CMR-FT strain values than patients with NAWMI . Global strain significantly improved at 4 months , especial in NAWMI. GLS was an independent predictor , followed by MVO  and GLS .CMR-FT-derived global myocardial strains significantly improved over time, especial in NAWMI. GLS measurement independently predicted the occurrence of medium-term MACE. ST-elevation myocardial infarction (STEMI) is an acute emergency that requires prompt reperfusion. Despite improvements in modern interventional and pharmacologic therapeutic treatment, some patients have unfavorable prognoses; therefore, valid risk stratification is crucial for STEMI ,2. VarioPrevious studies showed that patients with acute anterior wall myocardial infarction (AWMI) suffered more pronounced adverse LV remodeling and major adverse clinical events (MACE) than those with non-anterior wall myocardial infarction (NAWMI) ,6,7. HowThis retrospective study was approved by our hospital’s local ethics committee (No.XYFY2021-KL086-01), the study complied with the Declaration of Helsinki, and informed consent was waived by the committee because of the retrospective nature of this study. STEMI was defined on the basis of a history consistent with acute myocardial ischemia (prolonged chest pain lasting <12 h), ST-segments elevation on the ECG and elevated troponin I concentration. Patients with prior MI or revascularization, hemodynamic instability, atrial fibrillation, significant valvular heart disease, severe renal insufficiency, and conventional contraindication to CMR were excluded. All participants underwent emergent primary PCI and stent placement within 24 h of symptoms onset successfully.First-time acute STEMI who underwent primary PCI and two CMR examinations—one at day 4 (baseline) and the other at 4 months (follow-up)—after MI between September 2019 and March 2021 were included. The clinical endpoints were assessed by telephone interviews at 3, 6, and 12 weeks and every 6 months thereafter. The primary endpoint of the study was the occurrence of MACE, defined as recurrent angina pectoris, acute myocardial infarction, heart failure, and death due to coronary heart disease.CMR scans were performed on a 3.0T MR scanner . All images were acquired with electrocardiographic gating and breath holding. The protocol included steady-state free precession (SSFP), T2-weighted sequences, rest perfusion scans , and late-gadolinium enhancement (LGE) sequence 10–15 min after the administration of contrast agents. Both SSFP cine and LGE MR images were obtained including two-, three-, and four-chamber view images and a set of short-axis images covering the entire left ventricle from the atrioventricular ring to the apex. The SSFP sequence was obtained with 30 phases in the cardiac cycle; the parameters were as follows: field of view, 350*350 mm; repetition time/echo time (TR/TE), 2.6/1.3 ms; flip angle, 45°; and slice thickness, 8 mm. The LGE-CMR parameters were as follows: TR/TE, 3.0/ 6.1 ms; flip angle, 25°; and slice thickness, 8 mm.Anonymized CMR images were analyzed offline with a commercially available workstation  by two cardiac radiologists with 8- and 10- years’ experience respectively blinded to patient history and clinical outcome. The endocardial and epicardial borders were delineated manually in end diastolic images, wherein the software automatically tracks through the cardiac cycle.CMR-FT strain analysis was performed on four cine views, namely the two-, three-, four-chamber, and short-axis cine CMR images, and the peak value of radial strain, circumferential strain, and longitudinal strain was set as the GRS, GCS, and GLS respectively for statistical analysis. Left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and left ventricular ejection fraction (LVEF) were assessed from the short-axis cine images. MI represents the region of positive LGE, was automatically identified as the myocardium with signal intensity > 5SD mean signal intensity of remote myocardium. Manual delineation was used to quantify areas of hypointensity within the positive LGE, which represented microvascular obstruction (MVO) . The infContinuous variables are expressed as mean and SD or as median and interquartile range (IQR), while categorical variables are expressed as counts and percentages. For continuous variables, differences between the two groups were compared using Student’s t-tests or Mann–Whitney U tests, and categorical variables were compared by using the Fisher’s exact tests. Univariate and stepwise multivariate logistic regression analysis were used to identify predictors of MACE. Multivariate regression was performed using only variables that were p<0.1 in univariate regression analyses. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic accuracy of baseline strain parameters, IS, and MVO to predict the occurrence of outcome events at the clinical follow-up, the optimal cut-off values were identified by the Youden Index. All statistical analyses were performed with SPSS , and p<0.05 was considered statistically significant. The collinearity of the parameters is verified by variance inflation factor (VIF), and VIF < 5 indicates that there is no collinearity.A total of 103 patients with both baseline and follow-up CMR scans were enrolled in this study, including 48 and 55 patients with AWMI and NAWMI, respectively. The median age of the overall study group was 55 years (IQR: 47–65 years), and 87 (84.5%) patients were male. The baseline characteristics of the patients with AWMI and NAWMI are summarized in In the baseline CMR examination, a significant difference was observed in the LVEDV, LVEF, myocardial IS, MVO and all three LV strain parameters  between the AWMI and NAWMI groups .Follow-up CMR was completed at a median of 114 days (IQR: 100–123 days) after infarction. The GRS, GCS, and GLS all significantly improved from baseline to 4 months follow-up , and there was a certain effect of infarction location (AWMI vs. NAWMI) on GCS and GLS recovery  .At a median clinical follow-up of 18 months (IQR: 12–20 months), 15 patients (8 AWMI and 7 NAWMI) presented with MACE: recurrent MI (n = 9), repeated revascularization procedures by PCI (n = 5), and coronary artery bypass surgery (n = 1). There was no difference in the incidence rates of MACE between the AWMI and NAWMI groups. All characteristics in On the basis of area under the curve (AUC), baseline IS was the most accurate diagnostic parameter for MACE  = 0.731–0.932, p = 0.001), then AUC (MVO) = 0.812, 95% CI = 0.685–0.939, p<0.001, AUC (GLS) = 0.779, 95% CI = 0.644–0.914, p<0.001. The optimal cutoff values of GLS for MACE predictor was -7.9%, with sensitivity of 73.3% and specificity of 75.0%.The present study showed that AWMI patients suffer larger IS and MVO and worse EF and LV global strain than NAWMI patients. Global strains improved over time, especial in NAWMI. All three global strain measures  were associated with increased MACE rates; however, only GLS was an independent predictor of medium-term adverse clinical outcomes after MI. Further, IS remained the strongest predictor for medium-term MACE.According to the guidelines for the management of acute STEMI ,9, anterWhat’s more, both baseline and follow-up GRS, GCS, and GLS of AWMI were lower than NAWMI, and the recovery of GCS and GLS from baseline to 4 months later showed statistically significant differences between the AWMI and NAWMI groups. NAWMI patients showed better recovery than AWMI patients after MI. GCS and GLS are generally negative values by definition, and patients with less circumferential and longitudinal malformation always have a higher risk of adverse remodeling. Myocardial strain can be used to assess both global systolic function and systolic and diastolic function. Strain has substantial potential to be of diagnostic and prognostic value, and most of the clinical evidence for strain measurement is obtained by echocardiography . HoweverTo the best of our knowledge, there is no consensus regarding the association of CMR-FT parameters  with the highest risk of severe clinical events in the postinfarction period –20. In tIS and MVO measured by LGE are known to have added value as predictors of adverse outcomes after acute MI –24. MoreOur study has some limitations. First, we only included patients with hemodynamically stable and first-time STEMI; no critically ill patients were included. Thus, our results may not be generalizable to hemodynamically impaired, recurrent MI or non-STEMI patients. Second, this was a single-center study and the number of events was low, so further validation is required. Third, the majority of evidence and clinical experience regarding myocardial strain measures have been obtained by echocardiography in the past, however, in this study, due to the lack of echocardiography data in some patients, echocardiography indicators were not included in the study, this is also the disadvantage of retrospective study. Last, quantitative native T1 mapping, postcontrast T1 mapping, and extracellular volume quantification were not used in our study, which have been reported for improving post-STEMI risk stratification in the last few years.AWMI patients suffer worse LV global strain recovery than NAWMI, Acute IS, MVO and GLS measured by CMR-FT can independently predict medium-term MACE.S1 Data(XLSX)Click here for additional data file.