Correlation of Noninvasive Cardiac MRI Measures of Left Ventricular Myocardial Function and Invasive Pressure-Volume Parameters in a Porcine Ischemia-Reperfusion Model.

Purpose To assess the correlation between noninvasive cardiac MRI-derived parameters with pressure-volume (PV) loop data and evaluate changes in left ventricular function after myocardial infarction (MI). Materials and Methods Sixteen adult female swine were induced with MI, with six swine used as controls and 10 receiving platelet-derived growth factor-AB (PDGF-AB). Load-independent measures of cardiac function, including slopes of end-systolic pressure-volume relationship (ESPVR) and preload recruitable stroke work (PRSW), were obtained on day 28 after MI. Cardiac MRI was performed on day 2 and day 28 after infarct. Global longitudinal strain (GLS) and global circumferential strain (GCS) were measured. Ventriculo-arterial coupling (VAC) was derived from PV loop and cardiac MRI data. Pearson correlation analysis was performed. Results GCS (r = 0.60, P = .01), left ventricular ejection fraction (LVEF) (r = 0.60, P = .01), and cardiac MRI-derived VAC (r = 0.61, P = .01) had a significant linear relationship with ESPVR. GCS (r = 0.75, P < .001) had the strongest significant linear relationship with PRSW, followed by LVEF (r = 0.67, P = .005) and cardiac MRI-derived VAC (r = 0.60, P = .01). GLS was not significantly correlated with ESPVR or PRSW. There was a linear correlation (r = 0.82, P < .001) between VAC derived from cardiac MRI and from PV loop data. GCS (-3.5% ± 2.3 vs 0.5% ± 1.4, P = .007) and cardiac MRI-derived VAC (-0.6 ± 0.6 vs 0.3 ± 0.3, P = .001) significantly improved in the animals treated with PDGF-AB 28 days after MI compared with controls. Conclusion Cardiac MRI-derived parameters of MI correlated with invasive PV measures, with GCS showing the strongest correlation. Cardiac MRI-derived measures also demonstrated utility in assessing therapeutic benefit using PDGF-AB. Keywords: Cardiac MRI, Myocardial Infarction, Pressure Volume Loop, Strain Imaging, Ventriculo-arterial Coupling Supplemental material is available for this article. © RSNA, 2024.

Methodological identification of anomalies episodes in ECG streams: a systematic mapping study.

An electrocardiogram is a medical examination tool for measuring different patterns of heart blood flow circle either in the form of usual or non-invasive patterns. These patterns are useful for the identification of morbidity condition of the heart especially in certain conditions of heart abnormality and arrhythmia. Myocardial infarction (MI) is one of them that happened due to sudden blockage of blood by the cause of malfunction of heart. In electrocardiography (ECG) intensity of MI is highlighted on the basis of unusual patterns of T wave changes. Various studies have contributed for MI through T wave's classification, but more to the point of T wave has always attracted the ECG researchers. Methodology. This Study is primarily designed for proposing the combination of latest methods that are worked for the solutions of pre-defined research questions. Such solutions are designed in the form of the systematic review process (SLR) by following the Kitchen ham guidance. The literature survey is a two phase's process, at first phase collect the articles that were published in IEEE Xplore, Scopus, science direct and Springer from 2008 to 2023. It consist of steps; the first level is executed by filtrating the articles on the basis of keyword phase of title and abstract filter. Similarly, at two level the manuscripts are scanned through filter of eligibility criteria of articles selection. The last level belongs to the quality assessment of articles, in such level articles are rectified through evaluation of domain experts. Results. Finally, the selected articles are addressed with research questions and briefly discuss these selected state-of-the-art methods that are worked for the T wave classification. These address units behave as solutions to research problems that are highlighted in the form of research questions. Conclusion and future directions. During the survey process for these solutions, we got some critical observations in the form of gaps that reflected the other directions for researchers. In which feature engineering, different dependencies of ECG features and dimensional reduction of ECG for the better ECG analysis are reflection of future directions.

Evaluation of left ventricular blood flow kinetic energy in patients with acute myocardial infarction by 4D Flow MRI: a preliminary study.

PURPOSE: To evaluate the intracavity left ventricular (LV) blood flow kinetic energy (KE) parameters using four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) in patients with acute myocardial infarction (AMI). METHODS: Thirty AMI patients and twenty controls were examined via CMR, which included cine imaging, late gadolinium enhancement (LGE) and global heart 4D flow imaging. The KE parameters were indexed to LV end-diastolic volume (EDV) to obtain average, systolic and diastolic KE as well as the proportion of LV in-plane KE (%). These parameters were compared between the AMI patients and controls and between the two subgroups. RESULTS: Analysis of the LV blood flow KE parameters at different levels of the LV cavity and in different segments of the same level showed that the basal level had the highest blood flow KE while the apical level had the lowest in the control group. There were no significant differences in diastolic KE, systolic in-plane KE and diastolic in-plane KE between the anterior wall and posterior wall (p > 0.05), only the systolic KE had a significant difference between them (p < 0.05). Compared with those in the control group, the average (10.7 ± 3.3 µJ/mL vs. 14.7 ± 3.6 µJ/mL, p < 0.001), systolic (14.6 ± 5.1 µJ/mL vs. 18.9 ± 3.9 µJ/mL, p = 0.003) and diastolic KE (7.9 ± 2.5 µJ/mL vs. 10.6 ± 3.8 µJ/mL, p = 0.018) were significantly lower in the AMI group. The average KE in the infarct segment was lower than that in the noninfarct segment in the AMI group (49.5 ± 18.7 µJ/mL vs. 126.3 ± 50.7 µJ/mL, p < 0.001), while the proportion of systolic in-plane KE increased significantly (61.8%±11.5 vs. 42.9%±14.4, p = 0.001). CONCLUSION: The 4D Flow MRI technique can be used to quantitatively evaluate LV regional hemodynamic parameters. There were differences in the KE parameters of LV blood flow at different levels and in different segments of the same level in healthy people. In AMI patients, the average KE of the infarct segment decreased, while the proportion of systolic in-plane KE significantly increased.

Calcium signaling from sarcoplasmic reticulum and mitochondria contact sites in acute myocardial infarction.

Acute myocardial infarction (AMI) is a serious condition that occurs when part of the heart is subjected to ischemia episodes, following partial or complete occlusion of the epicardial coronary arteries. The resulting damage to heart muscle cells have a significant impact on patient's health and quality of life. About that, recent research focused on the role of the sarcoplasmic reticulum (SR) and mitochondria in the physiopathology of AMI. Moreover, SR and mitochondria get in touch each other through multiple membrane contact sites giving rise to the subcellular region called mitochondria-associated membranes (MAMs). MAMs are essential for, but not limited to, bioenergetics and cell fate. Disruption of the architecture of these regions occurs during AMI although it is still unclear the cause-consequence connection and a complete overview of the pathological changes; for sure this concurs to further damage to heart muscle. The calcium ion (Ca2+) plays a pivotal role in the pathophysiology of AMI and its dynamic signaling between the SR and mitochondria holds significant importance. In this review, we tried to summarize and update the knowledge about the roles of these organelles in AMI from a Ca2+ signaling point of view. Accordingly, we also reported some possible cardioprotective targets which are directly or indirectly related at limiting the dysfunctions caused by the deregulation of the Ca2+ signaling.

M2 macrophage-derived exosomes promote angiogenesis and improve cardiac function after myocardial infarction.

BACKGROUND: Myocardial infarction (MI) is a major cause of mortality and morbidity worldwide. The intercellular communication in post-infarction angiogenesis remains unclear. METHODS: In this study, we explored the role and mechanism of action of M2 macrophage-derived exosomes (M2-exos) in angiogenesis after MI. M2-exos were harvested and injected intramyocardially at the onset of MI. Two distinct endothelial cells (ECs) were cultured with M2-exos to explore the direct effects on angiogenesis. RESULTS: We showed that M2-exos improved cardiac function, reduced infarct size, and enhanced angiogenesis after MI. Moreover, M2-exos promoted angiogenesis in vitro; the molecules loaded in the vesicles were responsible for its proangiogenic effects. We further validated that higher abundance of miR-132-3p in M2-exos, which recapitulate their functions, was required for the cardioprotective effects exerted by M2-exos. Mechanistically, miR-132-3p carried by M2-exos down-regulate the expression of THBS1 through direct binding to its 3´UTR and the proangiogenic effects of miR-132-3p were largely reversed by THBS1 overexpression. CONCLUSION: Our findings demonstrate that M2-exos promote angiogenesis after MI by transporting miR-132-3p to ECs, and by binding to THBS1 mRNA directly and negatively regulating its expression. These findings highlight the role of M2-exos in cardiac repair and provide novel mechanistic understanding of intercellular communication in post-infarction angiogenesis.

Parameter subset reduction for imaging-based digital twin generation of patients with left ventricular mechanical discoordination.

BACKGROUND: Integration of a patient's non-invasive imaging data in a digital twin (DT) of the heart can provide valuable insight into the myocardial disease substrates underlying left ventricular (LV) mechanical discoordination. However, when generating a DT, model parameters should be identifiable to obtain robust parameter estimations. In this study, we used the CircAdapt model of the human heart and circulation to find a subset of parameters which were identifiable from LV cavity volume and regional strain measurements of patients with different substrates of left bundle branch block (LBBB) and myocardial infarction (MI). To this end, we included seven patients with heart failure with reduced ejection fraction (HFrEF) and LBBB (study ID: 2018-0863, registration date: 2019-10-07), of which four were non-ischemic (LBBB-only) and three had previous MI (LBBB-MI), and six narrow QRS patients with MI (MI-only) (study ID: NL45241.041.13, registration date: 2013-11-12). Morris screening method (MSM) was applied first to find parameters which were important for LV volume, regional strain, and strain rate indices. Second, this parameter subset was iteratively reduced based on parameter identifiability and reproducibility. Parameter identifiability was based on the diaphony calculated from quasi-Monte Carlo simulations and reproducibility was based on the intraclass correlation coefficient ( ICC ) obtained from repeated parameter estimation using dynamic multi-swarm particle swarm optimization. Goodness-of-fit was defined as the mean squared error ( χ 2 ) of LV myocardial strain, strain rate, and cavity volume. RESULTS: A subset of 270 parameters remained after MSM which produced high-quality DTs of all patients ( χ 2 < 1.6), but minimum parameter reproducibility was poor ( ICC min = 0.01). Iterative reduction yielded a reproducible ( ICC min = 0.83) subset of 75 parameters, including cardiac output, global LV activation duration, regional mechanical activation delay, and regional LV myocardial constitutive properties. This reduced subset produced patient-resembling DTs ( χ 2 < 2.2), while septal-to-lateral wall workload imbalance was higher for the LBBB-only DTs than for the MI-only DTs (p < 0.05). CONCLUSIONS: By applying sensitivity and identifiability analysis, we successfully determined a parameter subset of the CircAdapt model which can be used to generate imaging-based DTs of patients with LV mechanical discoordination. Parameters were reproducibly estimated using particle swarm optimization, and derived LV myocardial work distribution was representative for the patient's underlying disease substrate. This DT technology enables patient-specific substrate characterization and can potentially be used to support clinical decision making.

Cardiac function in a large animal model of myocardial infarction at 7 T: deep learning based automatic segmentation increases reproducibility.

Cardiac magnetic resonance (CMR) imaging allows precise non-invasive quantification of cardiac function. It requires reliable image segmentation for myocardial tissue. Clinically used software usually offers automatic approaches for this step. These are, however, designed for segmentation of human images obtained at clinical field strengths. They reach their limits when applied to preclinical data and ultrahigh field strength (such as CMR of pigs at 7 T). In our study, eleven animals (seven with myocardial infarction) underwent four CMR scans each. Short-axis cine stacks were acquired and used for functional cardiac analysis. End-systolic and end-diastolic images were labelled manually by two observers and inter- and intra-observer variability were assessed. Aiming to make the functional analysis faster and more reproducible, an established deep learning (DL) model for myocardial segmentation in humans was re-trained using our preclinical 7 T data (n = 772 images and labels). We then tested the model on n = 288 images. Excellent agreement in parameters of cardiac function was found between manual and DL segmentation: For ejection fraction (EF) we achieved a Pearson's r of 0.95, an Intraclass correlation coefficient (ICC) of 0.97, and a Coefficient of variability (CoV) of 6.6%. Dice scores were 0.88 for the left ventricle and 0.84 for the myocardium.

Clinical Value of Single-Projection Angiography-Derived FFR in Noninfarct-Related Artery.

BACKGROUND: The Murray law-based quantitative flow ratio (µFR) is an emerging technique that requires only 1 projection of coronary angiography with similar accuracy to quantitative flow ratio (QFR). However, it has not been validated for the evaluation of noninfarct-related artery (non-IRA) in acute myocardial infarction (AMI) settings. Therefore, our study aimed to evaluate the diagnostic accuracy of µFR and the safety of deferring non-IRA lesions with µFR >0.80 in the setting of AMI. METHODS: µFR and QFR were analyzed for non-IRA lesions of patients with AMI enrolled in the FRAME-AMI trial (Fractional Flow Reserve Versus Angiography-Guided Strategy for Management of Non-Infarction Related Artery Stenosis in Patients With Acute Myocardial Infarction), consisting of fractional flow reserve (FFR)-guided percutaneous coronary intervention and angiography-guided percutaneous coronary intervention groups. The diagnostic accuracy of µFR was compared with QFR and FFR. Patients were classified by the non-IRA µFR value of 0.80 as a cutoff value. The primary outcome was a vessel-oriented composite outcome, a composite of cardiac death, non-IRA-related myocardial infarction, and non-IRA-related repeat revascularization. RESULTS: µFR and QFR analyses were feasible in 443 patients (552 lesions). µFR showed acceptable correlation with FFR (R=0.777; P<0.001), comparable C-index with QFR to predict FFR ≤0.80 (µFR versus QFR: 0.926 versus 0.961, P=0.070), and shorter total analysis time (mean, 32.7 versus 186.9 s; P<0.001). Non-IRA with µFR >0.80 and deferred percutaneous coronary intervention had a significantly lower risk of vessel-oriented composite outcome than non-IRA with performed percutaneous coronary intervention (3.4% versus 10.5%; hazard ratio, 0.37 [95% CI, 0.14-0.99]; P=0.048). CONCLUSIONS: In patients with multivessel AMI, µFR of non-IRA showed acceptable diagnostic accuracy comparable to that of QFR to predict FFR ≤0.80. Deferred non-IRA with µFR >0.80 showed a lower risk of vessel-oriented composite outcome than revascularized non-IRA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02715518.

Myocardial infarction detection method based on the continuous T-wave area feature and multi-lead-fusion deep features.

Objective.Myocardial infarction (MI) is one of the most threatening cardiovascular diseases. This paper aims to explore a method for using an algorithm to autonomously classify MI based on the electrocardiogram (ECG).Approach.A detection method of MI that fuses continuous T-wave area (C_TWA) feature and ECG deep features is proposed. This method consists of three main parts: (1) The onset of MI is often accompanied by changes in the shape of the T-wave in the ECG, thus the area of the T-wave displayed on different heartbeats will be quite different. The adaptive sliding window method is used to detect the start and end of the T-wave, and calculate the C_TWA on the same ECG record. Additionally, the coefficient of variation of C_TWA is defined as the C_TWA feature of the ECG. (2) The multi lead fusion convolutional neural network was implemented to extract the deep features of the ECG. (3) The C_TWA feature and deep features of the ECG were fused by soft attention, and then inputted into the multi-layer perceptron to obtain the detection result.Main results.According to the inter-patient paradigm, the proposed method reached a 97.67% accuracy, 96.59% precision, and 98.96% recall on the PTB dataset, as well as reached 93.15% accuracy, 93.20% precision, and 95.14% recall on the clinical dataset.Significance.This method accurately extracts the feature of the C_TWA, and combines the deep features of the signal, thereby improving the detection accuracy and achieving favorable results on clinical datasets.

Reperfusion Injury in Patients With Acute Myocardial Infarction: JACC Scientific Statement.

Despite impressive improvements in the care of patients with ST-segment elevation myocardial infarction, mortality remains high. Reperfusion is necessary for myocardial salvage, but the abrupt return of flow sets off a cascade of injurious processes that can lead to further necrosis. This has been termed myocardial ischemia-reperfusion injury and is the subject of this review. The pathologic and molecular bases for myocardial ischemia-reperfusion injury are increasingly understood and include injury from reactive oxygen species, inflammation, calcium overload, endothelial dysfunction, and impaired microvascular flow. A variety of pharmacologic strategies have been developed that have worked well in preclinical models and some have shown promise in the clinical setting. In addition, there are newer mechanical approaches including mechanical unloading of the heart prior to reperfusion that are in current clinical trials.

Interval training suppresses nod-like receptor protein 3 inflammasome activation to improve cardiac function in myocardial infarction rats by hindering the activation of the transforming growth factor-ß1 pathway.

OBJECTIVE: Myocardial infarction (MI) -induced cardiac dysfunction can be attenuated by aerobic exercises. This study explored the mechanism of interval training (IT) regulating cardiac function in MI rats, providing some theoretical basis for clarifying MI pathogenesis and new ideas for clinically treating MI. METHODS: Rats were subjected to MI modeling, IT intervention, and treatments of the Transforming growth factor-ß1 (TGF-ß1) pathway or the nod-like receptor protein 3 (NLRP3) activators. Cardiac function and hemodynamic indicator alterations were observed. Myocardial pathological damage and fibrosis, reactive oxygen species (ROS) level, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities, MDA content, inflammasome-associated protein levels, and inflammatory factor levels were assessed. The binding between TGF-ß1 and receptor was detected. RESULTS: MI rats exhibited decreased left ventricle ejection fraction (LVEF), left ventricle fractional shortening  (LVFS), left ventricular systolic pressure  (LVSP), positive and negative derivates max/min (dP/dt max/min) and increased left ventricular end-systolic pressure (LVEDP), a large number of scar areas in myocardium, disordered cell arrangement and extensive fibrotic lesions, increased TGF-ß1 and receptor binding, elevated ROS level and MDA content and weakened SOD, CAT and GSH-Px activities, and up-regulated NLRP3, apoptosis-associated speck-like protein containing a CARD  (ASC) and cleaved-caspase-1 levels, while IT intervention caused ameliorated cardiac function. IT inactivated the TGF-ß1 pathway to decrease oxidative stress in myocardial tissues of MI rats and inhibit NLRP3 inflammasome activation. Activating NLRP3 partially reversed IT-mediated improvement on cardiac function in MI rats. CONCLUSION: IT diminished oxidative stress in myocardial tissues and suppressed NLRP3 inflammasome activation via inactivating the TGF-ß1 pathway, thus improving the cardiac function of MI rats.

Resident and recruited macrophages differentially contribute to cardiac healing after myocardial ischemia.

Cardiac macrophages are heterogenous in phenotype and functions, which has been associated with differences in their ontogeny. Despite extensive research, our understanding of the precise role of different subsets of macrophages in ischemia/reperfusion (I/R) injury remains incomplete. We here investigated macrophage lineages and ablated tissue macrophages in homeostasis and after I/R injury in a CSF1R-dependent manner. Genomic deletion of a fms-intronic regulatory element (FIRE) in the Csf1r locus resulted in specific absence of resident homeostatic and antigen-presenting macrophages, without affecting the recruitment of monocyte-derived macrophages to the infarcted heart. Specific absence of homeostatic, monocyte-independent macrophages altered the immune cell crosstalk in response to injury and induced proinflammatory neutrophil polarization, resulting in impaired cardiac remodeling without influencing infarct size. In contrast, continuous CSF1R inhibition led to depletion of both resident and recruited macrophage populations. This augmented adverse remodeling after I/R and led to an increased infarct size and deterioration of cardiac function. In summary, resident macrophages orchestrate inflammatory responses improving cardiac remodeling, while recruited macrophages determine infarct size after I/R injury. These findings attribute distinct beneficial effects to different macrophage populations in the context of myocardial infarction.

E-cardiac patch to sense and repair infarcted myocardium.

Conductive cardiac patches can rebuild the electroactive microenvironment for the infarcted myocardium but their repair effects benefit by carried seed cells or drugs. The key to success is the effective integration of electrical stimulation with the microenvironment created by conductive cardiac patches. Besides, due to the concerns in a high re-admission ratio of heart patients, a remote medicine device will underpin the successful repair. Herein, we report a miniature self-powered biomimetic trinity triboelectric nanogenerator with a unique double-spacer structure that unifies energy harvesting, therapeutics, and diagnosis in one cardiac patch. Trinity triboelectric nanogenerator conductive cardiac patches improve the electroactivity of the infarcted heart and can also wirelessly monitor electrocardiosignal to a mobile device for diagnosis. RNA sequencing analysis from rat hearts reveals that this trinity cardiac patches mainly regulates cardiac muscle contraction-, energy metabolism-, and vascular regulation-related mRNA expressions in vivo. The research is spawning a device that truly integrates an electrical stimulation of a functional heart patch and self-powered e-care remote diagnostic sensor.

Right Ventricular Myocardial Infarction-A Tale of Two Ventricles: JACC Focus Seminar 1/5.

Right ventricular infarction (RVI) complicates 50% of cases of acute inferior ST-segment elevation myocardial infarction, and is associated with high in-hospital morbidity and mortality. Ischemic right ventricular (RV) systolic dysfunction decreases left ventricular preload delivery, resulting in low-output hypotension with clear lungs, and disproportionate right heart failure. RV systolic performance is generated by left ventricular contractile contributions mediated by the septum. Augmented right atrial contraction optimizes RV performance, whereas very proximal occlusions induce right atrial ischemia exacerbating hemodynamic compromise. RVI is associated with vagal mediated bradyarrhythmias, both during acute occlusion and abruptly with reperfusion. The ischemic dilated RV is also prone to malignant ventricular arrhythmias. Nevertheless, RV is remarkably resistant to infarction. Reperfusion facilitates RV recovery, even after prolonged occlusion and in patients with severe shock. However, in some cases hemodynamic compromise persists, necessitating pharmacological and mechanical circulatory support with dedicated RV assist devices as a "bridge to recovery."

Activation of Cardiac δ2-Opioid Receptors Increases Heart Tolerance to Reperfusion.

Coronary occlusion (45 min) and reperfusion (120 min) in male Wistar rats in vivo, as well as total ischemia (45 min) of an isolated rat heart followed by reperfusion (30 min) were reproduced. The selective δ2-opioid receptor agonist deltorphin II (0.12 mg/kg and 152 nmol/liter) was administered intravenously 5 min before reperfusion in vivo or added to the perfusion solution at the beginning of reperfusion of the isolated heart. The peripheral opioid receptor antagonist naloxone methiodide and δ2-opioid receptor antagonist naltriben were used in doses of 5 and 0.3 mg/kg, respectively. It was found that the infarct-limiting effect of deltorphin II is associated with the activation of δ2-opioid receptors. We have demonstrated that deltorphin II can improve the recovery of the contractility of the isolated heart after total ischemia.

FEV1 and FVC as robust risk factors for cardiovascular disease and mortality: Insights from a large population study.

INTRODUCTION: Data is limited on influence of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) in a large adult population, including individuals with normal spirometry at baseline. METHODS: Using the UK Biobank cohort, a multivariable Cox regression analysis was conducted on 406,424 individuals to examine the association between FEV1 and FVC, categorized into three groups based on their percentage of predicted values (%pred) (≥80, 60-80 and < 60), and overall mortality, cardiovascular mortality, myocardial infarction, stroke, and heart failure over approximately 12.5 years. Moreover, a subgroup analysis was conducted on 295,459 individuals who had normal spirometry. RESULTS: Reduced FEV1 and FVC %pred values were associated with an elevated risk across all studied outcomes. Individuals with the lowest FEV1 and FVC %pred values (<60 %) exhibited HR of 1.83 (95 % CI 1.74-1.93) and 1.98 (95 % CI 1.76-2.22) for overall mortality, and 1.96 (95 % CI 1.83-2.1) and 2.26 (95 % CI 1.94-2.63) for cardiovascular mortality. Moreover, a graded association was observed between lower FEV1 and FVC %pred, even among never smokers and individuals with normal spirometry at baseline. DISCUSSION: Reduced FEV1 and FVC represent robust risk factors for cardiovascular disease and mortality. The fact that the increased risk was evident also at FEV1 and FVC levels exceeding 80 %pred challenges the contemporary classification of lung function categories and the notion that the entire FEV1- and FVC-range above 80 % of predicted represents a normal lung function.

Antiarrhythmic and Anti-Inflammatory Effects of Sacubitril/Valsartan on Post-Myocardial Infarction Scar.

BACKGROUND: Sacubitril/valsartan (Sac/Val) is superior to angiotensin-converting enzyme inhibitors in reducing the risk of heart failure hospitalization and cardiovascular death, but its mechanistic data on myocardial scar after myocardial infarction (MI) are lacking. The objective of this work was to assess the effects of Sac/Val on inflammation, fibrosis, electrophysiological properties, and ventricular tachycardia inducibility in post-MI scar remodeling in swine. METHODS: After MI, 22 pigs were randomized to receive ß-blocker (BB; control, n=8) or BB+Sac/Val (Sac/Val, n=9). The systemic immune response was monitored. Cardiac magnetic resonance data were acquired at 2-day and 29-day post MI to assess ventricular remodeling. Programmed electrical stimulation and high-density mapping were performed at 30-day post MI to assess ventricular tachycardia inducibility. Myocardial samples were collected for histological analysis. RESULTS: Compared with BB, BB+Sac/Val reduced acute circulating leukocytes (P=0.009) and interleukin-12 levels (P=0.024) at 2-day post MI, decreased C-C chemokine receptor type 2 expression in monocytes (P=0.047) at 15-day post MI, and reduced scar mass (P=0.046) and border zone mass (P=0.043). It also lowered the number and mass of border zone corridors (P=0.009 and P=0.026, respectively), scar collagen I content (P=0.049), and collagen I/III ratio (P=0.040). Sac/Val reduced ventricular tachycardia inducibility (P=0.034) and the number of deceleration zones (P=0.016). CONCLUSIONS: After MI, compared with BB, BB+Sac/Val was associated with reduced acute systemic inflammatory markers, reduced total scar and border zone mass on late gadolinium-enhanced magnetic resonance imaging, and lower ventricular tachycardia inducibility.