Chronic Myocardial Infarction Research Articles

Multivendor comparison of global and regional 2D cardiovascular magnetic resonance feature tracking strains vs tissue tagging at 3T

BackgroundCardiovascular magnetic resonance (CMR) 2D feature tracking (FT) left ventricular (LV) myocardial strain has seen widespread use to characterize myocardial deformation. Yet, validation of CMR FT measurements remains scarce, particularly for regional strain. Therefore, we aimed to perform intervendor comparison of 3 different FT software against tagging.MethodsIn 61 subjects (18 healthy subjects, 18 patients with chronic myocardial infarction, 15 with dilated cardiomyopathy, and 10 with LV hypertrophy due to hypertrophic cardiomyopathy or aortic stenosis) were prospectively compared global (G) and regional transmural peak-systolic Lagrangian longitudinal (LS), circumferential (CS) and radial strains (RS) by 3 FT software (cvi42, Segment, and Tomtec) among each other and with tagging at 3T. We also evaluated the ability of regional LS, CS, and RS by different FT software vs tagging to identify late gadolinium enhancement (LGE) in the 18 infarct patients.ResultsGLS and GCS by all 3 software had an excellent agreement among each other (ICC = 0.94–0.98 for GLS and ICC = 0.96–0.98 for GCS respectively) and against tagging (ICC = 0.92–0.94 for GLS and ICC = 0.88–0.91 for GCS respectively), while GRS showed inconsistent agreement between vendors (ICC 0.10–0.81). For regional LS, the agreement was good (ICC = 0.68) between 2 vendors but less vs the 3rd (ICC 0.50–0.59) and moderate to poor (ICC 0.44–0.47) between all three FT software and tagging. Also, for regional CS agreement between 2 software was higher (ICC = 0.80) than against the 3rd (ICC = 0.58–0.60), and both better agreed with tagging (ICC = 0.70–0.72) than the 3rd (ICC = 0.57). Regional RS had more variation in the agreement between methods ranging from good (ICC = 0.75) to poor (ICC = 0.05). Finally, the accuracy of scar detection by regional strains differed among the 3 FT software. While the accuracy of regional LS was similar, CS by one software was less accurate (AUC 0.68) than tagging (AUC 0.80, p < 0.006) and RS less accurate (AUC 0.578) than the other two (AUC 0.76 and 0.73, p < 0.02) to discriminate segments with LGE.ConclusionsWe confirm good agreement of CMR FT and little intervendor difference for GLS and GCS evaluation, with variable agreement for GRS. For regional strain evaluation, intervendor difference was larger, especially for RS, and the diagnostic performance varied more substantially among different vendors for regional strain analysis.

Bright-blood and dark-blood phase sensitive inversion recovery late gadolinium enhancement and T1 and T2 maps in a single free-breathing scan: an all-in-one approach

BackgroundQuantitative cardiovascular magnetic resonance (CMR) T1 and T2 mapping are used to detect diffuse disease such as myocardial fibrosis or edema. However, post gadolinium contrast mapping often lacks visual contrast needed for assessment of focal scar. On the other hand, late gadolinium enhancement (LGE) CMR which nulls the normal myocardium has excellent contrast between focal scar and normal myocardium but has poor ability to detect global disease. The objective of this work is to provide a calculated bright-blood (BB) and dark-blood (DB) LGE based on simultaneous acquisition of T1 and T2 maps, so that both diffuse and focal disease may be assessed within a single multi-parametric acquisition.MethodsThe prototype saturation recovery-based SASHA T1 mapping may be modified to jointly calculate T1 and T2 maps (known as multi-parametric SASHA) by acquiring additional saturation recovery (SR) images with both SR and T2 preparations. The synthetic BB phase sensitive inversion recovery (PSIR) LGE may be calculated from the post-contrast T1, and the DB PSIR LGE may be calculated from the post-contrast joint T1 and T2 maps. Multi-parametric SASHA maps were acquired free-breathing (45 heartbeats). Protocols were designed to use the same spatial resolution and achieve similar signal-to-noise ratio (SNR) as conventional motion corrected (MOCO) PSIR. The calculated BB and DB LGE were compared with separate free breathing (FB) BB and DB MOCO PSIR acquisitions requiring 16 and 32 heart beats, respectively. One slice with myocardial infarction (MI) was acquired with all protocols within 4 min.ResultsMultiparametric T1 and T2 maps and calculated BB and DB PSIR LGE images were acquired for patients with subendocardial chronic MI (n = 10), acute MI (n = 3), and myocarditis (n = 1). The contrast-to-noise (CNR) between scar (MI and myocarditis) and remote was 26.6 ± 7.7 and 20.2 ± 7.4 for BB and DB PSIR LGE, and 31.3 ± 10.6 and 21.8 ± 7.6 for calculated BB and DB PSIR LGE, respectively. The CNR between scar and the left ventricualr blood pool was 5.2 ± 6.5 and 29.7 ± 9.4 for conventional BB and DB PSIR LGE, and 6.5 ± 6.0 and 38.6 ± 11.6 for calculated BB and DB PSIR LGE, respectively.ConclusionsA single free-breathing acquisition using multi-parametric SASHA provides T1 and T2 maps and calculated BB and DB PSIR LGE images for comprehensive tissue characterization.

Role of Cardiac Magnetic Resonance (CMR) Imaging inthe Assessment of Wall Motion Abnormalities in MyocardialInfarction Patients

AbstractBackground: Subtle changes in left ventricular wall motionpatterns have diagnostic and prognostic values in patientswith Coronary Artery Disease (CAD).Aim of Study: The aim of this studywasto highlightthediagnostic role of Cardiac Magnetic Resonance imaging (CMR) in assessment of the myocardial wall motion abnor-malities in Myocardial Infarction (MI) patients.Material and Methods: This retrospective research wasperformed in 50 patients classified into two groups: Group 1(25 patients with Acute Myocardial Infarction (AMI) (23males and 2 females) and group 2 (25 patients with ChronicMyocardial Infarction (CMI) (22 males and 3 females). Bothclasses were diagnosed based on medical, echocardiography,and other approaches of cardiologist investigation. The meanage was 52.16±6.884 years for group 1 and 51.04±12.341years in group 2. All patients underwent CMR evaluationusing Cine Steady State Free Precession (SSFP) in short axisand 4 chamber views.Results: Hypokinesia was the most commonly observedwall motion abnormality among the study groups. It was seen in 13 (52%) patients in group 1 and the same in group 2. Akinesia was seen in 12 (48%) patients in group 1 and 10(48%) patients in group 2 and dyskinesia was observed in 2 (8%) patients in group 2 and not observed in group 1.Conclusion: Identification of wall motion abnormalitiesin MI patients may help to identify higher risk patients thatwould benefit from an earlier invasive strategy. We concludethat CMR detected the wall motion abnormality precisely andshould be added to the routine investigation of MI patientsfor better evaluation and assessment.

Cardiovascular magnetic resonance imaging of functional and microstructural changes of the heart in a longitudinal pig model of acute to chronic myocardial infarction

BackgroundWe examined the dynamic response of the myocardium to infarction in a longitudinal porcine study using relaxometry, functional as well as diffusion cardiovascular magnetic resonance (CMR). We sought to compare non contrast CMR methods like relaxometry and in-vivo diffusion to contrast enhanced imaging and investigate the link of microstructural and functional changes in the acute and chronically infarcted heart.MethodsCMR was performed on five myocardial infarction pigs and four healthy controls. In the infarction group, measurements were obtained 2 weeks before 90 min occlusion of the left circumflex artery, 6 days after ischemia and at 5 as well as 9 weeks as chronic follow-up. The timing of measurements was replicated in the control cohort. Imaging consisted of functional cine imaging, 3D tagging, T2 mapping, native as well as gadolinium enhanced T1 mapping, cardiac diffusion tensor imaging, and late gadolinium enhancement imaging.ResultsNative T1, extracellular volume (ECV) and mean diffusivity (MD) were significantly elevated in the infarcted region while fractional anisotropy (FA) was significantly reduced. During the transition from acute to chronic stages, native T1 presented minor changes (< 3%). ECV as well as MD increased from acute to the chronic stages compared to baseline: ECV: 125 ± 24% (day 6) 157 ± 24% (week 5) 146 ± 60% (week 9), MD: 17 ± 7% (day 6) 33 ± 14% (week 5) 29 ± 15% (week 9) and FA was further reduced: − 31 ± 10% (day 6) − 38 ± 8% (week 5) − 36 ± 14% (week 9). T2 as marker for myocardial edema was significantly increased in the ischemic area only during the acute stage (83 ± 3 ms infarction vs. 58 ± 2 ms control p < 0.001 and 61 ± 2 ms in the remote area p < 0.001). The analysis of functional imaging revealed reduced left ventricular ejection fraction, global longitudinal strain and torsion in the infarct group. At the same time the transmural helix angle (HA) gradient was steeper in the chronic follow-up and a correlation between longitudinal strain and transmural HA gradient was detected (r = 0.59 with p < 0.05). Comparing non-gadolinium enhanced data T2 mapping showed the largest relative change between infarct and remote during the acute stage (+ 33 ± 4% day 6, with p = 0.013 T2 vs. MD, p = 0.009 T2 vs. FA and p = 0.01 T2 vs. T1) while FA exhibited the largest relative change between infarct and remote during the chronic follow-up (+ 31 ± 2% week 5, with p = N.S. FA vs. MD, p = 0.03 FA vs. T2 and p = 0.003 FA vs. T1). Overall, diffusion parameters provided a higher contrast (> 23% for MD and > 27% for FA) during follow-up compared to relaxometry (T1 17–18%/T2 10–20%).ConclusionDuring chronic follow-up after myocardial infarction, cardiac diffusion tensor imaging provides a higher sensitivity for mapping microstructural alterations when compared to non-contrast enhanced relaxometry with the added benefit of providing directional tensor information to assess remodelling of myocyte aggregate orientations, which cannot be otherwise assessed.

Diagnostic and prognostic impact of cardiac magnetic resonance, including scar quantification and strain imaging in patients with malignant ventricular arrhythmias and nonobstructed coronary arteries

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Development and Innovation Fund of Hungary, National Research, Development and Innovation Office Background In case of malignant ventricular arrhythmias (VA) and nonobstructed coronary arteries, the differential diagnosis of the underlying diseases is still challenging, due to the board spectrum of possible causes. Cardiac magnetic resonance (CMR) provides functional, morphological and tissue specific information, including necrotic and scar-tissue. Aims We aimed to assess the diagnostic and prognostic implications of CMR parameters including global strain values and myocardial scar in patients after ventricular fibrillation (VF) or sustained ventricular tachycardia (SVT) and nonobstructed coronary arteries. Methods Between 2011 and 2019, 99 patients (42 ±17 years, 54 male) presenting with VF or SVT and nonobstructed coronary arteries, who underwent CMR examination before secondary prevention implantable cardioverter defibrillator (ICD) implantation were included in our study. Post-processing included feature-tracking strain analysis and left ventricular (LV) scar quantification. Patients were followed for the combined endpoint of all-cause-mortality and appropriate ICD therapy. Results CMR examination proved structural myocardial disease in 72%: dilated (n = 21), arrhythmogenic (n = 11), hypertrophic cardiomyopathy (n = 7) and other cardiomyopathies (n = 3). We found LGE patterns showing chronic myocardial infarction (n = 4), suggesting chronic myocarditis (n = 4) and aspecific nonischemic scar formation (n = 14). In 7 cases aspecific structural alterations without scar formation were detected. Overall, myocardial scar was found in 52%, with an average extent of 12 ± 8% of the LV myocardium. The CMR examination changed the clinical diagnosis in 55% of the patients. During a median follow-up at 2 years, 6 patients died and 42 experienced appropriate ICD therapy. We found an association between cardiac events and the presence of structural abnormality and myocardial scar (logrank: 4,553, p &amp;lt; 0.05 and 8.375, p &amp;lt;0.01). On Cox proportional-hazards modell LV ejection fraction, LV stroke volume index, the presence of structural abnormality, the presence and extent of myocardial scar, global LV strain parameters including longitudinal and circumferential strain, and a global left ventricular dssynchrony parameter (mechanical dispersion) were univariate predictors of the combined endpoint of all-cause-mortality and appropriate ICD therapy(p &amp;lt; 0.05). Conclusion CMR performed in patients after malignant VA and nonobstructed coronary arteries not only establishes the diagnosis in a high proportion of patients, but may also provide additional prognostic factors. This may indicate that CMR could play a complementary role in the risk stratification in this patient population. Abstract Figure.

Health Risks of Kretek Cigarettes: A Systematic Review.

IntroductionThe objective of this study is review the evidence on the health risks associated with smoking kretek cigarettes compared with not smoking or smoking regular cigarettes.MethodsWe conducted a systematic literature search in five electronic databases: EMBASE (Ovid), ASSIA, PubMed and Scopus. Since kretek use is largely restricted to Indonesia, we identified additional studies using an online search for grey literature and studies in Indonesian journals and the National Library of Indonesia. We included relevant search terms in English (“kretek” and “clove cigarettes”) and Bahasa (“rokok” and “merokok”). We selected studies which compared any health outcome between smokers of kretek cigarettes and non-smokers or smokers of regular cigarettes. We included studies in any smokers compared to non-smokers in Indonesia, since most Indonesian smokers use kretek, but analysed these separately. Study data were extracted by a single reviewer and checked by two reviewers. Methodological quality was assessed using the Newcastle-Ottawa scale.ResultsWe identified 32 studies, all from Indonesia. There were 31 cross-sectional studies and one case control study. This systematic review identified a relatively limited number of studies, and most of these were of poor quality as assessed by the Newcastle Ottawa score. They were generally cross-sectional, small and lacking justification for sample size, had high potential for selection bias because of lack of data on non-respondents or those lost to follow up, and missing information about the statistical analysis. Fourteen studies looked specifically at kretek exposure and eighteen looked at any type of cigarette exposure but were conducted in Indonesia are therefore likely to predominantly reflect kretek exposure. Kretek were found to be associated with oral cancer, cardiovascular disease, chronic health disease, myocardial infarction, asthma, and oral diseases.ConclusionsAlthough existing studies are of poor quality, kretek are likely to be at least as harmful as regular cigarettes.

Variation in the SERPINA6/SERPINA1 locus alters morning plasma cortisol, hepatic corticosteroid binding globulin expression, gene expression in peripheral tissues, and risk of cardiovascular disease

The stress hormone cortisol modulates fuel metabolism, cardiovascular homoeostasis, mood, inflammation and cognition. The CORtisol NETwork (CORNET) consortium previously identified a single locus associated with morning plasma cortisol. Identifying additional genetic variants that explain more of the variance in cortisol could provide new insights into cortisol biology and provide statistical power to test the causative role of cortisol in common diseases. The CORNET consortium extended its genome-wide association meta-analysis for morning plasma cortisol from 12,597 to 25,314 subjects and from ~2.2 M to ~7 M SNPs, in 17 population-based cohorts of European ancestries. We confirmed the genetic association with SERPINA6/SERPINA1. This locus contains genes encoding corticosteroid binding globulin (CBG) and α1-antitrypsin. Expression quantitative trait loci (eQTL) analyses undertaken in the STARNET cohort of 600 individuals showed that specific genetic variants within the SERPINA6/SERPINA1 locus influence expression of SERPINA6 rather than SERPINA1 in the liver. Moreover, trans-eQTL analysis demonstrated effects on adipose tissue gene expression, suggesting that variations in CBG levels have an effect on delivery of cortisol to peripheral tissues. Two-sample Mendelian randomisation analyses provided evidence that each genetically-determined standard deviation (SD) increase in morning plasma cortisol was associated with increased odds of chronic ischaemic heart disease (0.32, 95% CI 0.06–0.59) and myocardial infarction (0.21, 95% CI 0.00–0.43) in UK Biobank and similarly in CARDIoGRAMplusC4D. These findings reveal a causative pathway for CBG in determining cortisol action in peripheral tissues and thereby contributing to the aetiology of cardiovascular disease.

The relationship between ambient temperature and acute respiratory and cardiovascular diseases in Shenyang, China.

The purpose of this study was to analyze the acute effect of ambient temperature on hospitalization due to acute exacerbation of chronic obstructive pulmonary disease (AECOPD), stroke, and myocardial infarction (MI) in Shenyang, China. We used the distributed delayed nonlinear model to evaluate the impact of ambient temperature on respiratory and cardiovascular diseases. The study population was divided into four groups: < 65 group and ≥ 65 age groups, female and male groups. The < 65 age group of AECOPD patients was more likely to be affected by high ambient temperature, while the ≥ 65 age group of AECOPD patients was more sensitive to low ambient temperature. The hospitalization risk of MI admission increased in the ≥ 65 age group at 1–8 days delay under low ambient temperature conditions.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11356-020-11934-2.

Findings suggestive of coronary microvascular dysfunction in cats with myocardial ischemia.

Background:Myocardial infarction (MI) is an important cause of death and disability among humans worldwide. Few studies have reported the occurrence of MI in small animals as well. Reports in human medicine indicate that up to 30% of patients with clinical signs compatible with myocardial ischemia suggestive of coronary disease exhibit normal epicardial arteries at angiography. These symptoms have been associated with a syndrome characterized by alterations in cardiac microvasculature, known as coronary microvascular dysfunction (CMD). Aim:This study aimed to describe the necropsy findings and clinical-pathological characterization (when available) of cats with histopathological findings suggesting CMD. Methods:Necropsy records of cats presenting histopathological diagnosis compatible with acute and/or chronic MI, with normal epicardial arteries and microvascular disorders were evaluated.Results:Twenty animals met the inclusion criteria. Eight cats (40%) exhibited findings compatible with mild hypertrophic cardiomyopathy (HCM) without left atrial enlargement, one (5%) presented restrictive cardiomyopathy, and another one (5%) had lesions consistent with histiocytoid cardiomyopathy. The remaining cats (50%) showed alterations compatible with severe HCM with left atrial enlargement. In all cases, epicardial arteries were normal (without obstruction). All the evaluated hearts exhibited myocardial multifocal fibrosis along with replacement of cardiomyocytes by adipose tissue and blood vessels with hyperplasia and hypertrophy of the muscular layer with protrusion of the nuclei of the endothelial cells.Conclusion:These findings suggest the presence of microvascular dysplasia of the coronary arteries. Further studies are necessary to confirm and clinically characterize these results.

Chronic Stress and Risks for Myocardial Infarction in U.S. Adults

Long-term exposure to stress has been linked to multiple behavioral and biological responses that are detrimental to cardiovascular health, but the association between chronic stress and risks for acute myocardial infarction (MI) remains unknown. We examined the association between exposure to chronic stress and MI incidence from 2006 to 2016 using data from a nationally-representative prospective cohort study of adults aged 45 and older (n=15,109). Chronic stressors included ongoing issues related to personal health, social relationships, financial strain, housing, and caregiving responsibilities. Cox proportional hazards models were used to examine the association between the number of chronic stressors and MI while adjusting for confounding risk factors. More than half of the respondents reported ≥2 chronic stressors at baseline. Risks for MI increased incrementally from 1 chronic stressor (HR=1.28; 95% CI, 1.20-1.37) to ≥4 chronic stressors (HR = 2.71; 95% CI, 2.08-3.53) compared with those who reported no stressors. These risks were partly attenuated after adjustments for socioeconomic, psychosocial, behavioral, and clinical risk factors. The impact of chronic stressors was especially pronounced among adults with a history of MI (P value for interaction=.032). In adults with a prior MI, risks for a recurrent MI increased substantially from 1 chronic stressor (HR=1.31; 95% CI, 1.10-1.55) to ≥4 chronic stressors (HR = 2.92; 95% CI, 1.47-5.82) compared to those with no stressors. Chronic stress is a significant risk factor for acute coronary events in U.S. adults. More research is required to further understand the psychosocial, behavioral, and biological mechanisms underlying this association.

СЕРЦЕВО-СУДИННІ УСКЛАДНЕННЯ У ПАЦІЄНТІВ ІЗ COVID-19

Cardiovascular system is one of the most vulnerable during COVID-19. The main mechanisms of cardiac injury are: direct myocardial damage, mediated by viral binding to angiotensin-converting-ensyme-2, cardiac microvascular damage and thrombosis, caused by hypercoagulability. Cardiovascular complications such as acute and chronic myocardial injury, myocarditis, myocardial infarction, pulmonary embolism, stress-cardiomyopathy, arterial and venous thrombosis and arrhythmic disorders are common among COVID-19 patients. Myocardial injury in COVID-19 could have different mechanisms and may occur at early and late stages of the COVID-19 disease, resulting in myocardial dysfunction and heart failure. Echocardiography is a first-line noninvasive imaging method to assess the cardiac injury during COVID 19 while cardiac magnetic resonance imaging is the best to identify myocardial oedema, inflammation and fibrosis. In this article we presented the analysis of experience of cardiologists in different countries concerning diagnostics ant treatment of COVID-19 related cardiovascular pathology and case reports from our own experience concerning cardiovascular complications of COVID-19. Laboratory diagnostics (troponin and brain-natriuretic peptide) and noninvasive imaging methods (echocardiography and cardiac magnetic resonance tomography) are essential to confirm the diagnosis of cardiac injury in COVID-19 and to evaluate the effect of the treatment. Long-term follow-up studies are needed to understand better the COVID-19 related cardiac pathology.

Abstract 16617: Multimodality Imaging Approach in Delivery and Tracking of a Novel Imageable Hydrogel in a Chronic Porcine Infarct Model

Introduction: Left ventricular (LV) remodeling is a known complication from myocardial infarction (MI). Intramyocardial hydrogel (HG) delivery can potentially prevent LV remodeling post MI. We evaluated the feasibility of using multimodality imaging approach to assess the delivery and response to an imageable HG in a chronic porcine MI model. Methods: Nine Yorkshire pigs subjected to 90 min balloon occlusion and reperfusion were randomized 5 days post MI to delivery of HG (n=5) or controls (n=4). 99m Tc-Tetrofosmin was injected during the occlusion to assess risk area (RA). The imageable HG (Hyaluronic Acid/Gelatin modified with Aldehydes and Hydrazides, with 100 mg/mL iohexol) was delivered intramyocardially in a 3x3 grid 5 days post-MI after assessing MI region with Hybrid 201 Tl SPECT/CT. Contrast cineCT angiography was performed at baseline, 5 days post MI and 1 hour and 1 week post thoracotomy to assess LV geometry, HG location and CT intensity expressed as Hounsfield units (HU). Results: The average RA was 16.7% LV with no difference between the groups (p=0.44). The HG was delivered to the MI region with guidance of SPECT/CT. The HG was visible with cineCT post-delivery within perfusion defect (MI: 154 ± 26 HU; remote 82 ± 20 HU, p&lt;0.0001), but it was not visible 1 week post-delivery (MI: 79 ± 12 HU; remote 80 ± 14 HU, p=0.94). The wall thickening of the MI region dropped by 33% in both groups (p=0.99) at 5 days post MI. After HG delivery wall thickening increased by 33% in the HG group but decreased by 31% in the control group (HG: 2.42 ± 0.33 mm; Control: 1.25 ± 0.31 mm, p=0.041). After similar increase in end diastolic volume (EDV) 5 days post MI (p=0.43), the EVD was significantly reduced post HG delivery in the HG group (6.0 ± 2.0 ml reduction) compared to the control group (6.3 ± 4.4 ml increase, p=0.042). Conclusions: Multimodality imaging is a feasible method to guide and track the delivery of a novel imageable HG. Intramyocardial HG delivery was associated with decreased LV remodeling.

Silencing of METTL3 attenuates cardiac fibrosis induced by myocardial infarction via inhibiting the activation of cardiac fibroblasts.

Cardiac fibrosis is characterized by the activation of cardiac fibroblasts and accumulation of extracellular matrix. METTL3, a component of methyltransferase complex, participates in multiple biological processes associated with mammalian development and disease progression. However, the role of METTL3 in cardiac fibrosis is still unknown. We performed fibroblasts activation with TGF-β1 (20ng/mL) in vitro and established in vivo mouse models with lentivirus to assess the effects of METTL3 on cardiac fibroblasts proliferation and collagen formation. Methylated RNA immunoprecipitation (MeRIP) was used to define the potential fibrosis-regulated gene. The expression level of METTL3 was increased in cardiac fibrotic tissue of mice with chronic myocardial infarction and cultured cardiac fibroblats (CFs) treated with TGF-β1. Enforced expression of METTL3 promoted proliferation and fibroblast-to-myofibroblast transition and collagens accumulation, while silence of METTL3 did the opposite. Silence of METTL3 by lentivirus carrying METTL3 siRNA markedly alleviated cardiac fibrosis in MI mice. Transcriptome and N6-methyladenosine (m6 A) profiling analyses revealed that the expression and m6 A level of collagen-related genes were altered after silence of METTL3. METTL3-mediated m6 A modification is critical for the development of cardiac fibrosis, providing a molecular target for manipulating fibrosis and the associated cardiac diseases.

Outcomes of Percutaneous Coronary Intervention in Patients With Rheumatoid Arthritis

Rheumatoid arthritis (RA) is the most common inflammatory arthritis and is associated with increased risk of cardiovascular events and mortality. Evidence regarding outcomes following PCI is limited. This study aimed to assess differences in outcomes following percutaneous coronary intervention (PCI) between patients with and without RA. The Melbourne Interventional Group PCI registry (2005 to 2018) was used to identify 756 patients with RA. Outcomes were compared with the remaining cohort (n = 38,579). Patients with RA were older, more often female, with higher rates of hypertension, previous stroke, peripheral vascular disease, obstructive sleep apnea, chronic lung disease, myocardial infarction, and renal impairment, whereas rates of dyslipidemia and current smoking were lower, all p <0.05. Lesions in patients with RA were more frequently complex (ACC/AHA type B2/C), requiring longer stents, with higher rates of no reflow, all p <0.05. Risk of long-term mortality, adjusted for potential confounders, was higher for patients with RA (hazard ratio 1.53, 95% confidence interval 1.30 to 1.80; median follow-up 5.0 years), whereas 30-day outcomes including mortality, major adverse cardiovascular events, bleeding, stroke, myocardial infarction, coronary artery bypass surgery, and target vessel revascularization were similar. In subgroup analysis, patients with RA and lower BMI (Pfor interaction < 0.001) and/or acute coronary syndromes (Pfor interaction = 0.05) had disproportionately higher risk of long-term mortality compared with patients without RA. In conclusion, patients with RA who underwent PCI had more co-morbidities and longer, complex coronary lesions. Risk of short-term adverse outcomes was similar, whereas risk of long-term mortality was higher, especially among patients with acute coronary syndromes and lower body mass index.

Tissue factor cytoplasmic tail regulates myeloid cell derived superoxide formation and TGF-beta 1 driven cardiac remodeling in myocardial infarction

Abstract Background In the setting of myocardial infarction (MI), patients with coronary no-reflow and/or delayed presentation after onset of symptoms (sub-acute MI) are inflicted by severe thrombo-inflammation and are marked by worse clinical outcome. However, it is unclear whether tissue factor (TF) contributes to outcome post MI solely by the regulatory functions of its cytoplasmic tail independently of its coagulation activity. Purpose We analyzed the role of the TF cytoplasmic domain in the recruitment of myeloid cells into the infarcted myocardium and the consequences on cardiac remodeling, scar formation, development of heart failure and survival post MI. Methods Twelve Patients enrolled in the MICAT (Mainzer Intracoronary Database, ClinicalTrials.gov Identifier: NCT02180178) study were examined. Patients with sub-acute MI and stable coronary artery disease were defined and monocytes were isolated from peripheral blood mononuclear cells (PBMCs). Human heart samples acquired from the left ventricular wall of explanted hearts following cardiac transplantation or obtained during implantation of left ventricular assist device. Samples were investigated for downstream analysis of protein by western blots, RNA quantification and cryo-sectioning. MI was induced in 9 to 12 weeks old male C57BL/6J mice, mice specifically lacking the cytoplasmic tail (CT) of TF (TFΔCT mice) and TFfl/flLysMCre+/− mice by permanent ligation of the left anterior descending artery. Left ventricular function was assessed by High-Frequency Ultrasound System. Infiltration of immune cells into the infarcted myocardium was analyzed by performing flow cytometric analysis after enzymatic digestion of the myocardium. Superoxide levels were quantified by HPLC-based measurement of dihydroethidium derived oxidation product 2-hydroxy ethidium. Results Circulating monocytes in patients with sub-acute MI showed increased nitrosative stress as well as increased phosphorylation of TF CT along with TGF-β1 and NF-kB inflammatory activation, which was recapitulated in cardiac tissue of end-stage heart failure patients with chronic MI. MI results in phosphorylation of the CT of TF within myeloid cells. Using mice with conditional knockout of TF on myeloid cells or TFΔCT mice, we found that this regulatory intracellular domain of TF within myeloid cells is required for cardiac infiltration of inflammatory Ly6Chigh TF+ monocytes, Rac-1 GTPase and superoxide formation of gp91phox + myeloid cells in MI. TGF-β1 dependent SMAD2 activation and cardiac collagen deposition as late sequel of MI was reduced in TFΔCT mice, resulting in attenuated cardiac dysfunction and reduced mortality. Conclusion We conclude that, TF CT drives NADPH-oxidase derived superoxide formation, thrombo-inflammation and cardiac fibrosis. Therefore, it might serve as putative biomarker and risk predictor in MI Funding Acknowledgement Type of funding source: None

Relapse of chronic obstructive pulmonary disease and myocardial infarction: what is the connection?

Albeit largely underappreciated, chronic obstructive pulmonary disease (COPD) constitutes a major risk factor for cardiovascular diseases in general and for coronary disease in particular. The incidence of myocardial infarction, in fact increases rapidly, after relapse of COPD, with a peak event rate during the first week in the worst forms (those requiring hospitalization). Even though the precise mechanism is not completely defined, it is likely derived from two pathogenetic causes: (i) mismatch between myocardial demand and offer of O2 (not fully demonstrated and limited to few cases); (ii) acute coronary thrombosis, probably due to a systemic inflammatory reaction, brought upon by multiple interaction between the infective agent and the host immune system.

Microbial Peer Pressure: The Role of the Gut Microbiota in Hypertension and Its Complications.

There is increasing evidence of the influence of the gut microbiota on hypertension and its complications, such as chronic kidney disease, stroke, heart failure, and myocardial infarction. This is not surprising considering that the most common risk factors for hypertension, such as age, sex, medication, and diet, can also impact the gut microbiota. For example, sodium and fermentable fiber have been studied in relation to both hypertension and the gut microbiota. By combining second- and, now, third-generation sequencing with metabolomics approaches, metabolites, such as short-chain fatty acids and trimethylamine N-oxide, and their producers, have been identified and are now known to affect host physiology and the cardiovascular system. The receptors that bind these metabolites have also been explored with positive findings-examples include known short-chain fatty acid receptors, such as G-protein coupled receptors GPR41, GPR43, GPR109a, and OLF78 in mice. GPR41 and OLF78 have been shown to have inverse roles in blood pressure regulation, whereas GPR43 and GPR109A have to date been demonstrated to impact cardiac function. New treatment options in the form of prebiotics (eg, dietary fiber), probiotics (eg, Lactobacillus spp.), and postbiotics (eg, the short-chain fatty acids acetate, propionate, and butyrate) have all been demonstrated to be beneficial in lowering blood pressure in animal models, but the underlying mechanisms remain poorly understood and translation to hypertensive patients is still lacking. Here, we review the evidence for the role of the gut microbiota in hypertension, its risk factors, and cardiorenal complications and identify future directions for this exciting and fast-evolving field.

Development and validation of coding algorithms to identify patients with incident lung cancer in United States healthcare claims data.

Our aim was to develop and validate a practical US healthcare claims algorithm for identifying incident lung cancer that improves on positive predictive value (PPV) and sensitivity observed in past studies. Patients newly diagnosed with lung cancer in Surveillance, Epidemiology, and End Results (SEER) (gold standard) were linked with Medicare claims. A 5% Medicare "other cancer" sample and noncancer sample served as controls. A split-sample validation approach was used. Rules-based, regression, and machine learning models for developing algorithms were explored. Algorithms were developed in the model building subset. Rules-based algorithms and those with the highest F scores were evaluated in the validation subset. F scores were compared for 1000 bootstrap samples. Misclassification was evaluated by calculating the odds of selection by the algorithm among true positives and true negatives. A practical single-score algorithm derived from a logistic regression model had sensitivity = 78.22% and PPV = 78.50% (F score: 78.36). The algorithm was most likely to misclassify older patients (ages ≥80 years) or with missing data in the SEER registry, shorter follow-up time in Medicare (<3 months), insurance through Veterans Affairs, >1 cancer in SEER, or certain Charlson comorbidities (dementia, chronic pulmonary disease, liver disease, or myocardial infarction). In this dataset, a practical point-based algorithm for identifying incident lung cancer demonstrated significant and substantial improvement (7.9% and 23.9% absolute improvement in sensitivity and PPV, respectively) compared with a current standard.

Myocardial Infarction Severity Stages Classification From ECG Signals Using Attentional Recurrent Neural Network

Myocardial infarction (MI) is a lethal heart condition that occurs due to the lack of blood flow to the heart tissues. Based on the time from symptoms onset, it is categorized into three severity stages: early MI (EMI), acute MI (AMI), and chronic MI (CMI). Electrocardiogram (ECG) signals are often used to diagnose MI with pathological changes in its characteristics. In clinical practice, accurate diagnosis and risk-stratification are essential to optimize various treatment strategies, hence clinical outcome. However, most automated methods focus only on identifying MI patients from healthy controls (HC). Therefore, in this paper, we propose a novel multi-lead diagnostic attention-based recurrent neural network (MLDA-RNN) for automated diagnosis of the three MI severity stages from HC subjects. The method systematically processes the 12-lead ECGs to capture the multi-scale temporal dependencies from each ECG leads for improved classification. Specifically, we first employ the RNNs to encode the temporal variations in the 12-lead ECG signals. These encoded vectors are fed to the intra-lead attention module to summarize the within-lead discriminative vectors to obtain lead-attentive representations. Then, the inter-lead attention module aggregates these representative vectors based on their clinical relevance to obtain a high-level feature representation for a reliable diagnosis. Using 12-lead ECGs from the PTBDB and STAFF III datasets, we achieved an overall accuracy of 97.79% without compromising on the class-wise detection rates. With improved performance, the MLDA-RNN also shows promising results for model interpretability as the learned attention weights often correlate with clinicians' way of diagnosing MI severity stages.

NFκB promotes oxidative stress-induced necrosis and ischemia/reperfusion injury by inhibiting Nrf2-ARE pathway

In this study, we identified an unexpected pro-cell death role for NFκB in mediating oxidative stress-induced necrosis, and provide new mechanistic evidence that NFκB, in cooperation with HDAC3, negatively regulates Nrf2-ARE anti-oxidative signaling through transcriptional silencing. We showed that genetic inactivation of NFκB-p65 inhibited, whereas activation of NFκB promoted, oxidative stress-induced cell death and HMGB1 release, a biomarker of necrosis. Moreover, NFκB-luciferase activity was elevated in cardiomyocytes after simulated ischemia/reperfusion (sI/R) or doxorubicin (DOX) treatment, and inhibition of NFκB with Ad-p65-shRNA or Ad-IκBαM diminished sI/R- and DOX-induced cell death and HMGB1 release. Importantly, NFκB negatively regulated Nrf2-ARE activity and the expression of antioxidant proteins. Mechanistically, co-immunoprecipitation revealed that p65 was required for Nrf2-HDAC3 interaction and transcriptional silencing of Nrf2-ARE activity. Further, the ability of HDAC3 to repress Nrf2-ARE activity was lost in p65 deficient cells. Pharmacologic inhibition of HADCs or NFκB with trichostatin A (TSA) or BMS-345541, respectively, increased Nrf2-ARE activity and promoted cell survival after sI/R. In vivo, NFκB transcriptional activity in the mouse heart was significantly elevated after ischemia/reperfusion (I/R) injury, which was abolished by cardiomyocyte-specific deletion of p65 using p65fl/flNkx2.5-Cre mice. Moreover, genetic ablation of p65 in the mouse heart attenuated myocardial infarct size after acute I/R injury and improved cardiac remodeling and functional recovery after chronic myocardial infarction. Thus, our results identified NFκB as a key regulator of oxidative stress-induced necrosis by suppressing the Nrf2-ARE antioxidant pathway through an HDAC3-dependent mechanism. This study also revealed a new pathogenic role of NFκB in cardiac ischemic injury and pathological remodeling.