Chronic Myocardial Infarction Research Articles

Cardiovascular Risk Factors and Secondary Events Among Acute and Chronic Stable Myocardial Infarction Patients: Findings from a Managed Care Database.

IntroductionLong-term risk for recurrent cardiovascular events among myocardial infarction (MI) patients in the acute versus chronic stable phase is not well characterized. This study was conducted to evaluate risk factors associated with all-cause mortality and cardiovascular (CVD) morbidity and to determine the transition period from the acute to chronic stable phase of disease.MethodsAdministrative claims data from a managed care database (2007–2012) were linked to the Social Security Death Index. Kaplan–Meier curves were generated over a 3-year period. The association between risk factors and clinical endpoints was assessed using Cox proportional hazard models. Poisson models estimated the ‘transition time’ from acute to chronic phase of disease.ResultsOn average, recurrent cardiovascular event rates were higher among acute MI patients in comparison to the chronic MI patients during the first 3 months of follow-up. Over the 3-year follow-up period, survival curves became parallel and for some outcomes (i.e., acute myocardial infarction and bleeding events), were not statistically significantly different between the two groups. In both the acute and chronic MI cohorts, diabetes, heart failure, and renal disease were consistently statistically significant and positively associated with greater risk of death and ischemic events. PAD was consistently associated with increased risk among the chronic cohort and composite endpoints among the acute patients.ConclusionsGreater understanding of differences in the CVD risk profiles and the transition from acute to chronic stable phase may help identify high-risk patients and inform clinical risk stratification and long-term disease management in MI patients.FundingMerck & Co., Inc., Kenilworth, NJ, USA.Electronic supplementary materialThe online version of this article (10.1007/s40119-019-00147-5) contains supplementary material, which is available to authorized users.

Cardiac intramural electrical mapping reveals focal delays but no conduction velocity slowing in the peri-infarct region.

Altered electrical behavior alongside healed myocardial infarcts (MIs) is associated with increased risk of sudden cardiac death. However, the multidimensional mechanisms are poorly understood and described. This study characterizes, for the first time, the intramural spread of electrical activation in the peri-infarct region of chronic reperfusion MIs. Four sheep were studied 13 wk after antero-apical reperfusion infarction. Extracellular potentials (ECPs) were recorded in a ~20 × 20-mm2 region adjacent to the infarct boundary (25 plunge needles <0.5-mm diameter with 15 electrodes at 1-mm centers) during multisite stimulation. Infarct geometry and electrode locations were reconstructed from magnetic resonance images. Three-dimensional activation spread was characterized by local activation times and interpolated ECP fields (n = 191 records). Control data were acquired in 4 non-infarcted sheep (n = 96 records). Electrodes were distributed uniformly around 15 ± 5% of the intramural infarct boundary. There were marked changes in pacing success and ECP morphology across a functional border zone (BZ) ±2 mm from the boundary. Stimulation adjacent to the infarct boundary was associated with low-amplitude electrical activity within the BZ and delayed activation of surrounding myocardium. Bulk tissue depolarization occurred 3.5-14.6 mm from the pacing site for 39% of stimuli with delays of 4-37 ms, both significantly greater than control (P < 0.0001). Conduction velocity (CV) adjacent to the infarct was not reduced compared with control, consistent with structure-only computer model results. Insignificant CV slowing, irregular stimulus-site specific activation delays, and obvious indirect activation pathways strongly suggest that the substrate for conduction abnormalities in chronic MI is predominantly structural in nature.NEW & NOTEWORTHY Intramural in vivo measurements of peri-infarct electrical activity were not available before this study. We use pace-mapping in a three-dimensional electrode array to show that a subset of stimuli in the peri-infarct region initiates coordinated myocardial activation some distance from the stimulus site with substantial associated time delays. This is site dependent and heterogeneous and occurs for <50% of ectopic stimuli in the border zone. Furthermore, once coordinated activation is initiated, conduction velocity adjacent to the infarct boundary is not significantly different from control. These results give new insights to peri-infarct electrical activity and do not support the widespread view of uniform electrical remodeling in the border zone of chronic myocardial infarcts, with depressed conduction velocity throughout.

Arrhythmia development during inhibition of small-conductance calcium-activated potassium channels in acute myocardial infarction in a porcine model.

Acute myocardial infarction (AMI) is associated with intracellular Ca2+ build-up. In healthy ventricles, small conductance Ca2+-activated K+ (SK) channels are present but do not participate in repolarization. However, SK current is increased in chronic myocardial infarction and heart failure, and recently, SK channel inhibition was demonstrated to reduce arrhythmias in AMI rats. Hence, we hypothesized that SK channel inhibitors (NS8593 and AP14145) could reduce arrhythmia development during AMI in a porcine model. Twenty-seven pigs were randomized 1:1:1 to control, NS8593, or AP14145. Haemodynamic and electrophysiological parameters [electrocardiogram (ECG) and monophasic action potentials (MAP)] were continuously recorded. A balloon was placed in the mid-left anterior descending artery, blinded to treatment. Infusion lasted from 10 min before occlusion until 30 min after. Occlusion was maintained for 1 h, followed by 2 h of reperfusion. Upon occlusion, cardiac output dropped similarly in all groups, while blood pressure remained stable. Heart rate decreased in the NS8593 and AP14145 groups. QRS duration increased upon occlusion in all groups but more prominently in AP14145-treated pigs. Inhibition of SK channels did not affect QT interval. Infarct MAP duration shortened comparably in all groups. Ventricular fibrillation developed in 4/9 control-, 4/9 AP14145-, and 2/9 NS8593-treated pigs. Ventricular tachycardia was rarely observed in either group, whereas ventricular extrasystoles occurred comparably in all groups. Inhibition of SK channels was neither beneficial nor detrimental to ventricular arrhythmia development in the setting of AMI in this porcine model.

Accurate identification of myocardial viability after myocardial infarction with novel manganese chelate-based MR imaging.

We developed a novel manganese (Mn2+ ) chelate for magnetic resonance imaging (MRI) assessment of myocardial viability in acute and chronic myocardial infarct (MI) models, and compared it with Gadolinium-based delay enhancement MRI (Gd3+ -DEMRI) and histology. MI was induced in 14 rabbits by permanent occlusion of the left circumflex coronary artery. Gd3+ -DEMRI and Mn2+ chelate-based delayed enhancement MRI (Mn2+ chelate-DEMRI) were performed at 7days (acute MI, n=8) or 8weeks (chronic MI, n=6) after surgery with sequential injection of 0.15mmol/kg Gd3+ and Mn2+ chelate. The biodistribution of Mn2+ in tissues and blood was measured at 1.5 and 24h. Blood pressure, heart rate (HR), left ventricular (LV) function, and infarct fraction (IF) were analyzed, and IF was compared with the histology. The Mn2+ chelate group maintained a stable hemodynamic status during experiment. For acute and chronic MI, all rabbits survived without significant differences in HR or LV function before and after injection of Mn2+ chelate or Gd3+ (p>0.05). Mn2+ chelate mainly accumulated in the kidney, liver, spleen, and heart at 1.5h, with low tissue uptake and urine residue at 24h after injection. In the acute MI group, there was no significant difference in IF between Mn2+ chelate-DEMRI and histology (22.92±2.21% vs. 21.79±2.25%, respectively, p=0.87), while Gd3+ -DEMRI overestimated IF, as compared with histology (24.54±1.73%, p=0.04). In the chronic MI group, there was no significant difference in IF between the Mn2+ chelate-DEMRI, Gd3+ -DEMRI, and histology (29.50±11.39%, 29.95±9.40%, and 29.00±10.44%, respectively, p>0.05), and all three were well correlated (r=0.92-0.96, p<0.01). We conclude that the use of Mn2+ chelate-DEMRI is reliable for MI visualization and identifies acute MI more accurately than Gd3+ -DEMRI.

Value of myocardial scar in predicting malignant ventricular arrhythmia in patients with chronic myocardial infarction

To assess the predictive value of myocardial scar mass in malignant ventricular arrhythmia (MVA) after myocardial infarction. Thirty myocardial infarction patients with complete electrophysiology and cardiac MRI data admitted from January 2012 to August 2017 were enrolled in the study. According to the results of intracavitary electrophysiological study, MVA developed in 16 patients (MVA group) and not developed in 14 patients (non-MVA group). The qualitative and quantitative analysis of left ventricular ejection fraction (LVFE) and scar mass was performed with CVI42 post-processing software and predictive value of myocardial scar and LVEF for MVA after myocardial infarction was analyzed using ROC curves. LVEF in MVA group was significantly lower than that in non-MVA group, and scar mass in MVA group was significantly higher than that in non-MVA group (all P<0.05). Regression analysis showed that LVEF (OR=1.580) and scar mass (OR=6.270) were risk factors for MVA after myocardial infarction. For predicting MVA, the area under ROC curve (AUC) of LVEF was 0.696 with a sensitivity of 0.786 and the specificity of 0.685; the AUC of the scar mass was 0.839 with a sensitivity was 0.618 and the specificity of 0.929; the AUC of LVEF combined with scar mass was 0.848 with a sensitivity of 0.688 and specificity of 0.857. Myocardial scar assessed by late gadolinium enhancement MRI is more effective than LVEF in predicting MVA after myocardial infarction.

Design of the patient navigator to Reduce Readmissions (PArTNER) study: A pragmatic clinical effectiveness trial

Previous work indicates the potential for community health workers and peer coaches serving as patient navigators to improve processes of care and health outcomes during care transitions, but have not been sufficiently tested to determine if such programs improve measures of patient experience in minority serving institutions. The objectives of the Patient Navigator to Reduce Readmissions (PArTNER) study was to: 1) conduct a pragmatic clinical effectiveness trial comparing a multi-faceted, stakeholder-supported Navigator intervention (in-person CHW visits in the hospital and after hospital discharge, plus telephone-based peer coaching) versus usual care on the experience of hospital-to-home care transitions in patients hospitalized with heart failure, pneumonia, chronic obstructive pulmonary disease, myocardial infarction, or sickle cell disease; 2) examine the effectiveness of the Navigator intervention in patient subgroups; and 3) understand the barriers and facilitators of successfully implementing the Navigator intervention across patient populations. The co-primary outcomes are the 30-day changes in: 1) Patient Reported Outcomes Measurement Information System (PROMIS) emotional distress-anxiety, and 2) PROMIS informational support. Secondary outcomes at 30 and 60 days include other PROMIS health measures and hospital readmissions. Innovative features of the PArTNER study include early and continuous engagement of patients, their caregivers, clinicians, health system administrators, and other stakeholders to inform the design and implementation of the Navigator intervention. In this report, we describe the design of the PArTNER study.

Long-term exposure to PM2.5 and ozone and hospital admissions of Medicare participants in the Southeast USA

We examined the association between average annual fine particulate matter (PM2.5) and ozone and first hospital admissions of Medicare participants for stroke, chronic obstructive pulmonary disease (COPD), pneumonia, myocardial infarction (MI), lung cancer, and heart failure (HF). Annual average PM2.5 and ozone levels were estimated using high-resolution spatio-temporal models. We fit a marginal structural Cox proportional hazards model, using stabilized inverse probability weights (IPWs) to account for the competing risk of death and confounding. Analyses were then repeated after restricting to exposure levels below the current U.S. standards. The results showed that PM2.5 was significantly associated with an increased hazard of admissions for all studied outcomes; the highest observed being a 6.1% (95% CI: 5.9%–6.2%) increase in the hazard of admissions with pneumonia for each μg/m3 increase in particulate levels. Ozone was also significantly associated with an increase in the risk of first hospital admissions of all outcomes. The hazard of pneumonia increased by 3.0% (95% CI: 2.9%–3.1%) for each ppb increase in the ozone level. Our results reveal a need to regulate long-term ozone exposure, and that associations persist below current PM2.5 standards.

P128Acute on chronic thromboembolic myocardial infarction - thrombus age assessment by multi-modality cardiac imaging

P128Acute on chronic thromboembolic myocardial infarction - thrombus age assessment by multi-modality cardiac imaging

Association between Sleep Duration and Chronic Rhinosinusitis among the Korean General Adult Population: Korea National Health and Nutrition Examination Survey

An association between sleep duration and a wide spectrum of diseases has been reported, but little is known about its relationship with chronic rhinosinusitis (CRS). The present study aimed to investigate whether sleep duration was associated with CRS after adjusting for potential confounding factors in Korean adults. We analyzed data from the Korea National Health and Nutrition Examination Survey 2005–2009 and enrolled 24,658 participants aged ≥20 years. Data regarding sociodemographic characteristics, self-reported sleep duration, CRS, and other medical diseases were collected from questionnaires. Multiple logistic regression analyses were used to identify the relationship between sleep duration and CRS. The overall prevalence of CRS was 4.4%. Subjects with sleep duration ≤5 hours showed a highest prevalence for CRS (6.1%), compared to subjects with longer sleep duration (p = 0.02). After adjusting for covariates (age, sex, household income, residency, dwelling type, education, depression, alcohol, allergic rhinitis, chronic otitis media, angina or myocardial infarction, asthma, chronic obstructive pulmonary disease, bronchiectasis, and gastric ulcer), the sleep duration of ≤5 hours was significantly associated with CRS (OR = 1.502; 95% CI = 1.164–1.938). Only in older subgroup (≥50 years old), shorter sleep duration (≤5 hours) showed higher odds for CRS. These results suggested that sleep duration may be negatively associated with CRS in older Korean adults.

The effect of air pollution on hospitalization of individuals with respiratory and cardiovascular diseases in Jinan, China

To analyze the short-term effects of air pollution on the hospitalization rates of individuals with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), stroke, and myocardial infarction (MI) after adjusting for confounding factors including weather, day of the week, holidays, and long-term trends in Jinan, China.Hospitalization information was extracted based on data from the primary class 3-A hospitals in Jinan from 2013 to 2015. The concentrations of PM2.5, PM10, SO2, NO2, and O3 were obtained from Jinan Environment Monitoring Center. The relative risk and 95% confidence intervals of AECOPD, stroke, and MI were estimated using generalized additive models with quasi-Poisson distribution in the mgcv package, using R software, version 1.0.136.The incremental increased concentrations of particulate pollutants including PM2.5 and PM10 were significantly associated with increased risk of hospitalization of AECOPD, stroke, and MI, and the adverse influences of PM2.5 on these diseases were generally stronger than that of PM10. The incremental increased concentrations of gaseous pollutants including SO2, NO2, and O3 were significantly associated with increased risk of hospitalization of stroke and MI in this population.Air pollution has significant adverse effects on hospitalization rates of individuals with AECOPD, stroke, and MI in Jinan, China.

Deep Learning for Diagnosis of Chronic Myocardial Infarction on Nonenhanced Cardiac Cine MRI.

Background Renal impairment is common in patients with coronary artery disease and, if severe, late gadolinium enhancement (LGE) imaging for myocardial infarction (MI) evaluation cannot be performed. Purpose To develop a fully automatic framework for chronic MI delineation via deep learning on non-contrast material-enhanced cardiac cine MRI. Materials and Methods In this retrospective single-center study, a deep learning model was developed to extract motion features from the left ventricle and delineate MI regions on nonenhanced cardiac cine MRI collected between October 2015 and March 2017. Patients with chronic MI, as well as healthy control patients, had both nonenhanced cardiac cine (25 phases per cardiac cycle) and LGE MRI examinations. Eighty percent of MRI examinations were used for the training data set and 20% for the independent testing data set. Chronic MI regions on LGE MRI were defined as ground truth. Diagnostic performance was assessed by analysis of the area under the receiver operating characteristic curve (AUC). MI area and MI area percentage from nonenhanced cardiac cine and LGE MRI were compared by using the Pearson correlation, paired t test, and Bland-Altman analysis. Results Study participants included 212 patients with chronic MI (men, 171; age, 57.2 years ± 12.5) and 87 healthy control patients (men, 42; age, 43.3 years ± 15.5). Using the full cardiac cine MRI, the per-segment sensitivity and specificity for detecting chronic MI in the independent test set was 89.8% and 99.1%, respectively, with an AUC of 0.94. There were no differences between nonenhanced cardiac cine and LGE MRI analyses in number of MI segments (114 vs 127, respectively; P = .38), per-patient MI area (6.2 cm2 ± 2.8 vs 5.5 cm2 ± 2.3, respectively; P = .27; correlation coefficient, r = 0.88), and MI area percentage (21.5% ± 17.3 vs 18.5% ± 15.4; P = .17; correlation coefficient, r = 0.89). Conclusion The proposed deep learning framework on nonenhanced cardiac cine MRI enables the confirmation (presence), detection (position), and delineation (transmurality and size) of chronic myocardial infarction. However, future larger-scale multicenter studies are required for a full validation. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Leiner in this issue.

IL33 attenuates ventricular remodeling after myocardial infarction through inducing alternatively activated macrophages ethical standards statement

Interleukin 33 (IL33) has been found to be cardioprotective on various cardiovascular pathologies. However, it is not clear whether IL33 may inhibit myocardial infarction-related ventricular remodeling through inducing macrophage polarization. The objective of present study is to assess whether IL33 can improve ventricular remodeling after myocardial infarction by inducing macrophage polarization.In this study, the direct influence of IL33 on the polarization of macrophages and its mechanism in vitro were investigated. The potential protective effects of IL33 on acute and chronic myocardial infarction (MI) in vivo as well as its underlying mechanism through macrophage polarization were also determined.We found that IL33 significantly enhanced M2 macrophage and decreased the proportion of M1 macrophage. Importantly, IL33 induced M2 macrophage polarization by activating the JAK/STAT signaling pathway. In vivo, IL33 weaken the inflammatory level and myocardial apoptosis after MI and improved the systolic and diastolic function of the heart. Furthermore, IL33 significantly reduced infarct area and prevented the progression of fibrosis by inducing M2 macrophage polarization. The protective effects of IL33 were suppressed by JAK/STAT signaling pathway inhibitor.Our findings highlighted that IL33 not only reduced the early inflammatory response and inhibited myocardial apoptosis, but also increased the number of M2 macrophage in the infarcted area, significantly reduced infarct area and prevented the progression of fibrosis by activating JAK/STAT pathway. Therefore, IL33 may be a novel cardiac protective cytokine for myocardial infarction.

Smoking, drinking, diet and physical activity-modifiable lifestyle risk factors and their associations with age to first chronic disease.

BackgroundThis study examined the incidence of a person’s first diagnosis of a selected chronic disease, and the relationships between modifiable lifestyle risk factors and age to first of six chronic diseases.MethodsOntario respondents from 2001 to 2010 of the Canadian Community Health Survey were followed up with administrative data until 2014 for congestive heart failure, chronic obstructive respiratory disease, diabetes, lung cancer, myocardial infarction and stroke. By sex, the cumulative incidence function of age to first chronic disease was calculated for the six chronic diseases individually and compositely. The associations between modifiable lifestyle risk factors (alcohol, body mass index, smoking, diet, physical inactivity) and age to first chronic disease were estimated using cause-specific Cox proportional hazards models and Fine-Gray competing risk models.ResultsDiabetes was the most common disease. By age 70.5 years (2015 world life expectancy), 50.9% of females and 58.1% of males had at least one disease and few had a death free of the selected diseases (3.4% females; 5.4% males). Of the lifestyle factors, heavy smoking had the strongest association with the risk of experiencing at least one chronic disease (cause-specific hazard ratio = 3.86; 95% confidence interval = 3.46, 4.31). The lifestyle factors were modelled for each disease separately, and the associations varied by chronic disease and sex.ConclusionsWe found that most individuals will have at least one of the six chronic diseases before dying. This study provides a novel approach using competing risk methods to examine the incidence of chronic diseases relative to the life course and how their incidences are associated with lifestyle behaviours.

Hypoxic-conditioned cardiosphere-derived cell sheet transplantation for chronic myocardial infarction.

Cell therapy provides a suitable environment for regeneration through paracrine effects such as secretion of growth factors. Cardiosphere-derived cells (CDCs) have a high capacity for growth factor secretion and are an attractive target for clinical applications. In particular, a cell sheet technique was reported to have clinical advantages by covering a specific region. Here, we examined the effect of the hypoxic-conditioned (HC) autologous CDC sheet therapy on a rabbit chronic myocardial infarction model. CDC sheet function was assessed by the enzyme-linked immunosorbent assay and quantified by polymerase chain reaction in vitro (days 1-3 of conditioning). The rabbit chronic myocardial infarction model was established by left coronary ligation. Autologous CDCs were isolated from the left atrial specimen; CDC sheets with or without 2-day HC were transplanted onto the infarcted hearts at 4 weeks. The cardiac function was assessed by an echocardiography at 0, 4 and 8 weeks. A histological analysis of the host hearts was performed by tomato lectin staining at 8 weeks. The optimal HC duration was 48 h. HC significantly increased the mRNA expression levels of VEGF and ANG2 on day 2 compared to the normoxic-conditioned (NC) group. The HC group showed significant improvement in the left ventricular ejection fraction (64.4% vs 58.8% and 53.4% in the NC and control) and a greater lectin-positive area in the ischaemic region (HC:NC:control = 13:8:2). HC enhances the paracrine effect of a CDC sheet on angiogenesis to improve cardiac function in the chronic myocardial infarction model, which is essential for cardiomyocyte proliferation during cardiac regeneration.

Pioglitazone strengthen therapeutic effect of adipose-derived regenerative cells against ischemic cardiomyopathy through enhanced expression of adiponectin and modulation of macrophage phenotype

BackgroundThe efficacy of cell transplantation in heart failure is reportedly modest, but adjuvant drugs combined with cell therapy may improve this efficacy. Peroxisome proliferator-activated receptor (PPAR)γ, one of the hypoglycemic medicine for diabetes mellitus, reportedly enhances cytokine production in adipose tissue-derived regenerative cells (ADRCs). We hypothesized that combined administration of PPARγ agonists and ADRCs may enhance the paracrine effects of adiponectin (APN), leading to functional recovery in a chronic myocardial infarction (MI) model.MethodsADRCs were isolated from adipose tissues of adult rats by gradient centrifugation and embedded in bio-compatible fibrin-glue to produce ADRCs grafts. In the in vitro study, the ADRCs grafts released APN, which was significantly enhanced by the PPARγ agonist (PGZ, pioglitazone). Transplantation of ADRCs grafts (group A), ADRCs mixed with PGZ (group AP), APN knockdown-ADRCs (group Si) or PGZ (group P) onto the epicardium or a sham operation (group C) was performed (n = 10–20 per group).ResultsThe AP group showed significant improvement in ejection fraction compared to that in the other groups. In the AP group, a significantly larger number of M2-polarized macrophages was detected and existed for a significantly longer duration in the infarct area. Furthermore, comparing Si group and P group, western blotting of T-cadherin revealed that exogenous APN and local expression of T-cadherin were essential to this histological change and recovery of cardiac function.ConclusionsCombined administration of PPARγ agonist and ADRSCs activated M2-polarized macrophages with enhancement of APN paracrine effects and lead to better cardiac function in a rat infarction model.

Yes-associated protein (YAP) mediates adaptive cardiac hypertrophy in response to pressure overload

Cardiovascular disease (CVD) remains the leading cause of death globally, and heart failure is a major component of CVD-related morbidity and mortality. The development of cardiac hypertrophy in response to hemodynamic overload is initially considered to be beneficial; however, this adaptive response is limited and, in the presence of prolonged stress, will transition to heart failure. Yes-associated protein (YAP), the central downstream effector of the Hippo signaling pathway, regulates proliferation and survival in mammalian cells. Our previous work demonstrated that cardiac-specific loss of YAP leads to increased cardiomyocyte (CM) apoptosis and impaired CM hypertrophy during chronic myocardial infarction (MI) in the mouse heart. Because of its documented cardioprotective effects, we sought to determine the importance of YAP in response to acute pressure overload (PO). Our results indicate that endogenous YAP is activated in the heart during acute PO. YAP activation that depended upon RhoA was also observed in CMs subjected to cyclic stretch. To examine the function of endogenous YAP during acute PO, Yap+/flox;Creα-MHC (YAP-CHKO) and Yap+/flox mice were subjected to transverse aortic constriction (TAC). We found that YAP-CHKO mice had attenuated cardiac hypertrophy and significant increases in CM apoptosis and fibrosis that correlated with worsened cardiac function after 1 week of TAC. Loss of CM YAP also impaired activation of the cardioprotective kinase Akt, which may underlie the YAP-CHKO phenotype. Together, these data indicate a prohypertrophic, prosurvival function of endogenous YAP and suggest a critical role for CM YAP in the adaptive response to acute PO.

Convolutional neural network-based approach for segmentation of left ventricle myocardial scar from 3D late gadolinium enhancement MR images.

Accurate three-dimensional (3D) segmentation of myocardial replacement fibrosis (i.e., scar) is emerging as a potentially valuable tool for risk stratification and procedural planning in patients with ischemic cardiomyopathy. The main purpose of this study was to develop a semiautomated method using a 3D convolutional neural network (CNN)-based for the segmentation of left ventricle (LV) myocardial scar from 3D late gadolinium enhancement magnetic resonance (LGE-MR) images. Our proposed CNN is built upon several convolutional and pooling layers aimed at choosing appropriate features from LGE-MR images to distinguish between myocardial scar and healthy tissues of the left ventricle. In contrast to previous methods that consider image intensity as the sole feature, CNN-based algorithms have the potential to improve the accuracy of scar segmentation through the creation of unconventional features that separate scar from normal myocardium in the feature space. The first step of our pipeline was to manually delineate the left ventricular myocardium, which was used as the region of interest for scar segmentation. Our developed algorithm was trained using 265,220 volume patches extracted from ten 3D LGE-MR images, then was validated on 450,454 patches from a testing dataset of 24 3D LGE-MR images, all obtained from patients with chronic myocardial infarction. We evaluated our method in the context of several alternative methods by comparing algorithm-generated segmentations to manual delineations performed by experts. Our CNN-based method reported an average Dice similarity coefficient (DSC) and Jaccard Index (JI) of 93.63%±2.6% and 88.13%±4.70%. In comparison to several previous methods, including K-nearest neighbor (KNN), hierarchical max flow (HMF), full width at half maximum (FWHM), and signal threshold to reference mean (STRM), the developed algorithm reported significantly higher accuracy for DSC with a P-value less than 0.0001. Our experimental results demonstrated that our CNN-based proposed method yielded the highest accuracy of all contemporary LV myocardial scar segmentation methodologies, inclusive of the most widely used signal intensity-based methods, such as FWHM and STRM. To our knowledge, this is the first description of LV myocardial scar tissue segmentation from 3D LGE-MR images using a CNN-based method.

Texture analysis of myocardial infarction in CT: Comparison with visual analysis and impact of iterative reconstruction

ObjectivesTo compare texture analysis (TA) with subjective visual diagnosis of myocardial infarction (MI) in cardiac computed tomography (CT) and to evaluate the impact of iterative reconstruction (IR). MethodsTen patients (4 women, mean age 68 ± 11 years) with confirmed chronic MI and 20 controls (8 women, mean age 52 ± 11 years) with no cardiac abnormality underwent contrast-enhanced cardiac CT with the same protocol. Images were reconstructed with filtered back projection (FBP) and with advanced modeled IR at strength levels 3–5. Subjective diagnosis of MI was made by three independent, blinded readers with different experience levels. Classification of MI was performed using machine learning–based decision tree models for the entire data set and after splitting into training and test data to avoid overfitting. ResultsSubjective visual analysis for diagnosis of MI showed excellent intrareader (kappa: 0.93) but poor interreader agreement (kappa: 0.3), with variable performance at different image reconstructions. TA showed high performance for all image reconstructions (correct classifications: 94%–97%, areas under the curve: 0.94–0.99). After splitting into training and test data, overall lower performances were observed, with best results for IR at level 5 (correct classifications: 73%, area under the curve: 0.65). ConclusionsAs compared with subjective, nonreliable visual analysis of inexperienced readers, TA enables objective and reproducible diagnosis of chronic MI in cardiac CT with higher accuracy. IR has a considerable impact on both subjective and objective image analysis.

Water-fat separation and parameter mapping in cardiac MRI via deep learning with a convolutional neural network.

Water-fat separation is a postprocessing technique most commonly applied to multiple-gradient-echo magnetic resonance (MR) images to identify fat, provide images with fat suppression, and to measure fat tissue concentration. Recently, Numerous advancements have been reported. In contrast to early methods, the process of water-fat separation has become complicated due to multiparametric analytic models, optimization methods, and the absence of a unified framework for diverse source data. To determine the feasibility and performance of MRI water-fat separation and parametric mapping via deep learning (DL) with a range of inputs. Retrospective data usage. Ninety cardiac MR examinations from normal control, acute, subacute, and chronic myocardial infarction subjects were obtained, providing 1200 multiple gradient-echo acquisitions. 1.5 T/2D multiple gradient-echo pulse sequence ASSESSMENT: Ground-truth training and validation water-fat separation were obtained using a graph cut method with R2 *, off-resonance correction, and a multipeak fat spectrum. U-Net DL training with single and multiecho, complex, and magnitude inputs were compared using quantitative and three-observer subjective analysis. DL methods' image structural similarity, and quantitative proton density fat fraction (PDFF), R2 *, and off-resonance quantitative values were statistically compared with the GraphCut reference standard using Student's t-test and Pearson's correlation. Myocardial fat deposition in chronic myocardial infarction and intramyocardial hemorrhage in acute myocardial infarction were well visualized in the DL results. Predicted values for R2 *, off-resonance, water, and fat signal intensities were well correlated with a conventional model-based water fat separation (R2 ≥ 0.97, P < 0.001) with appropriate inputs. DL parameter maps had a 14% higher signal-to-noise ratio (P < 0.001) when compared with a conventional method. DL water-fat separation is feasible with a wide range of inputs, while R2 * and off-resonance mapping requires multiple echoes and complex images. With appropriate inputs, DL provides quantitative and subjective results comparable to conventional model-based methods. 1 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019;50:655-665.

Calcium Sensitizing and Phosphodiesterase-III Inhibitory Activity of Pyridazine Compounds: A Review

Congestive heart disease is one of the main causes of death in the globe, affecting more than 1% of the world population. Various remedial agents are used for the treatment of cardiac diseases such as inotropics and vasodilators. Sympathomimetic drugs play an important role, but they unfortunately undergo severely from oral ineffectiveness and tachyphylaxis due to receptor desensitization. Recently, several cardiac phasphodiestrase-III (PDE-III) inhibitors have been developed with improved ventricular performance and exercise tolerances. Theoretically, PDE-inhibitors combine positive inotropy and vasodilation (known as zinodilator) action and these exceptional features make them very attractive. Various pyridazine drugs act as selective PDE-III inhibitor and characterized by a positive inotropic effect combined with vasodilatory effects. The pyridazine is an important heterocyclic structure with various biologically active compounds with diverse pharmacological activities. Pyridazine hold considerable interest relative to the physiologically active cardiac compounds such as Ca+2 sensitizing and PDE-III inhibitor activity. However, some pyridazine compounds have been reported as effective agents in the treatment of several cardiovascular diseases including, acute and chronic heart failure, myocardial infarction, angina, arrhythmia, and hypertension. Pyridazinone nucleus has focus attention because of new pyridazinone compounds will design and development of novel Ca+2 sensitizing and PDE-III inhibitors as cardio tonic agents in future.