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Intrinsic and Extrinsic Cardiac Pseudotumors: Echocardiographic Evaluation and Review of the Literature. - Echocardiography (Mount Kisco, N.Y.)
Echocardiography is the most common imaging modality for the assessment of cardiovascular tumors, followed by more advanced imaging modalities, such as cardiac computed tomography or cardiac magnetic resonance imaging. Non-neoplastic lesions that may simulate a true neoplasm on imaging are termed "cardiac pseudotumors." As echocardiography is the initial imaging modality where pseudotumors are identified, it is imperative to have a fundamental understanding of pseudotumors evaluation using echocardiography. There is paucity of the literature describing the different kinds of pseudotumors. This review is an attempt to describe common cardiac pseudotumors and to classify them based on their origin. The tumors arising from cardiac structures, such as epicardium, endocardium, or myocardium, were termed as "intrinsic" while the pseudotumors with no cardiac origin were termed as "extrinsic." The more common pseudotumors are described in detail with pertinent echocardiographic features and examples.Â© 2015, Wiley Periodicals, Inc.
Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men. - European heart journal
There is a significant uncertainty regarding the effect of testosterone replacement therapy (TRT) on cardiovascular (CV) outcomes including myocardial infarction (MI) and stroke. The aim of this study was to examine the relationship between normalization of total testosterone (TT) after TRT and CV events as well as all-cause mortality in patients without previous history of MI and stroke.We retrospectively examined 83 010 male veterans with documented low TT levels. The subjects were categorized into (Gp1: TRT with resulting normalization of TT levels), (Gp2: TRT without normalization of TT levels) and (Gp3: Did not receive TRT). By utilizing propensity score-weighted Cox proportional hazard models, the association of TRT with all-cause mortality, MI, stroke, and a composite endpoint was compared between these groups. The all-cause mortality [hazard ratio (HR): 0.44, confidence interval (CI) 0.42-0.46], risk of MI (HR: 0.76, CI 0.63-0.93), and stroke (HR: 0.64, CI 0.43-0.96) were significantly lower in Gp1 (n = 43 931, median age = 66 years, mean follow-up = 6.2 years) vs. Gp3 (n = 13 378, median age = 66 years, mean follow-up = 4.7 years) in propensity-matched cohort. Similarly, the all-cause mortality (HR: 0.53, CI 0.50-0.55), risk of MI (HR: 0.82, CI 0.71-0.95), and stroke (HR: 0.70, CI 0.51-0.96) were significantly lower in Gp1 vs. Gp2 (n = 25 701, median age = 66 years, mean follow-up = 4.6 years). There was no difference in MI or stroke risk between Gp2 and Gp3.In this large observational cohort with extended follow-up, normalization of TT levels after TRT was associated with a significant reduction in all-cause mortality, MI, and stroke.Published by Oxford University Press on behalf of the European Society of Cardiology 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Generation of Functional Cardiomyocytes from Efficiently Generated Human iPSCs and a Novel Method of Measuring Contractility. - PloS one
Human induced pluripotent stem cells (iPSCs) derived cardiomyocytes (iCMCs) would provide an unlimited cell source for regenerative medicine and drug discoveries. The objective of our study is to generate functional cardiomyocytes from human iPSCs and to develop a novel method of measuring contractility of CMCs. In a series of experiments, adult human skin fibroblasts (HSF) and human umbilical vein endothelial cells (HUVECs) were treated with a combination of pluripotent gene DNA and mRNA under specific conditions. The iPSC colonies were identified and differentiated into various cell lineages, including CMCs. The contractile activity of CMCs was measured by a novel method of frame-by-frame cross correlation (particle image velocimetry-PIV) analysis. Our treatment regimen transformed 4% of HSFs into iPSC colonies at passage 0, a significantly improved efficiency compared with use of either DNA or mRNA alone. The iPSCs were capable of differentiating both in vitro and in vivo into endodermal, ectodermal and mesodermal cells, including CMCs with >88% of cells being positive for troponin T (CTT) and Gata4 by flow cytometry. We report a highly efficient combination of DNA and mRNA to generate iPSCs and functional iCMCs from adult human cells. We also report a novel approach to measure contractility of iCMCs.
Monocyte Chemoattractant Protein-Induced Protein 1 (MCPIP1) Enhances Angiogenic and Cardiomyogenic Potential of Murine Bone Marrow-Derived Mesenchymal Stem Cells. - PloS one
The current evidence suggests that beneficial effects of mesenchymal stem cells (MSCs) toward myocardial repair are largely due to paracrine actions of several factors. Although Monocyte chemoattractant protein-induced protein 1 (MCPIP1) is involved in the regulation of inflammatory response, apoptosis and angiogenesis, whether MCPIP1 plays any role in stem cell-induced cardiac repair has never been examined. By employing retroviral (RV)-transduced overexpression of MCPIP1, we investigated the impact of MCPIP1 on viability, apoptosis, proliferation, metabolic activity, proteome, secretome and differentiation capacity of murine bone marrow (BM) - derived MSCs. MCPIP1 overexpression enhanced angiogenic and cardiac differentiation of MSCs compared with controls as indicated by elevated expression of genes accompanying angiogenesis and cardiomyogenesis in vitro. The proangiogenic activity of MCPIP1-overexpressing MSCs (MCPIP1-MSCs) was also confirmed by increased capillary-like structure formation under several culture conditions. This increase in differentiation capacity was associated with decreased proliferation of MCPIP1-MSCs when compared with controls. MCPIP1-MSCs also expressed increased levels of proteins involved in angiogenesis, autophagy, and induction of differentiation, but not adverse inflammatory agents. We conclude that MCPIP1 enhances endothelial and cardiac differentiation of MSCs. Thus, modulating MCPIP1 expression may be a novel approach useful for enhancing the immune-regulatory, anti-apoptotic, anti-inflammatory and regenerative capacity of BM-derived MSCs for myocardial repair and regeneration of ischemic tissues.
Role of Outpatient Cardiac Rhythm Monitoring in Cryptogenic Stroke: A Systematic Review and Meta-Analysis. - Pacing and clinical electrophysiology : PACE
Recent studies have suggested that prolonged outpatient rhythm monitoring results in increased detection of atrial fibrillation (AF) in patients with cryptogenic stroke (CS). However, the best monitoring strategy and its clinical utility is debatable.To compare the effectiveness of implantable loop recorder (ILR) versus wearable devices in identifying AF in patients with CS.Three randomized controlled trials (RCTs) and 13 observational studies were identified by database searches. Seven studies (enrolling 774 patients) employed ILR for AF detection for a median duration of 365 days (range 50-569 days). Ten studies (enrolling 996 patients) employed continuous monitoring with wearable devices for a median duration of 21 days (range 4-30 days). One study performed 7 days of monitoring with wearable device followed by implantation of ILR, thus included in both groups. Pooled odds ratio (OR) of identifying AF in RCTs showed increased detection of AF with prolonged monitoring (OR 4.54, 95% confidence interval [CI] 2.92, 7.06; P < 0.00001) compared to routine outpatient follow-up. Overall detection of AF with outpatient monitoring was 17.6% (CI: 12.5-22.7). There was significantly higher AF detection with ILR (23.3%; CI: 13.83-32.29) compared to wearable devices (13.6%; CI: 7.91-19.32; P < 0.05). Patients with AF were older in age compared to patients without AF.AF detection in patients with CS is improved with prolonged rhythm monitoring and is better with ILR compared to wearable devices. AF was more common in older patients. The clinical significance of these findings is unknown at this point.Â© 2015 Wiley Periodicals, Inc.
Adult Bone Marrow Cell Therapy for Ischemic Heart Disease: Evidence and Insights From Randomized Controlled Trials. - Circulation research
Notwithstanding the uncertainties about the outcomes of bone marrow cell (BMC) therapy for heart repair, further insights are critically needed to improve this promising approach.To delineate the true effect of BMC therapy for cardiac repair and gain insights for future trials through systematic review and meta-analysis of data from eligible randomized controlled trials.Database searches through August 2014 identified 48 eligible randomized controlled trials (enrolling 2602 patients). Weighted mean differences for changes in left ventricular (LV) ejection fraction, infarct size, LV end-systolic volume, and LV end-diastolic volume were analyzed with random-effects meta-analysis. Compared with standard therapy, BMC transplantation improved LV ejection fraction (2.92%; 95% confidence interval, 1.91-3.92; P<0.00001), reduced infarct size (-2.25%; 95% confidence interval, -3.55 to -0.95; P=0.0007) and LV end-systolic volume (-6.37 mL; 95% confidence interval, -8.95 to -3.80; P<0.00001), and tended to reduce LV end-diastolic volume (-2.26 mL; 95% confidence interval, -4.59 to 0.07; P=0.06). Similar effects were noted when data were analyzed after excluding studies with discrepancies in reporting of outcomes. The benefits also persisted when cardiac catheterization was performed in control patients as well. Although imaging modalities partly influenced the outcomes, LV ejection fraction improved in BMC-treated patients when assessed by magnetic resonance imaging. Early (<48 hours) BMC injection after myocardial Infarction was more effective in reducing infarct size, whereas BMC injection between 3 and 10 days proved superior toward improving systolic function. A minimum of 50 million BMCs seemed to be necessary, with limited additional benefits seen with increasing cell numbers. BMC therapy was safe and improved clinical outcomes, including all-cause mortality, recurrent myocardial Infarction, ventricular arrhythmia, and cerebrovascular accident during follow-up, albeit with differences between acute myocardial Infarction and chronic ischemic heart disease subgroups.Transplantation of adult BMCs improves LV ejection fraction, reduces infarct size, and ameliorates remodeling in patients with ischemic heart disease. These effects are upheld in the analyses of studies using magnetic resonance imaging and also after excluding studies with discrepant reporting of outcomes. BMC transplantation may also reduce the incidence of death, recurrent myocardial Infarction, ventricular arrhythmia, and cerebrovascular accident during follow-up.Â© 2015 American Heart Association, Inc.
Epigenetic modifiers reduce inflammation and modulate macrophage phenotype during endotoxemia-induced acute lung injury. - Journal of cell science
Acute lung injury (ALI) during sepsis is characterized by bilateral alveolar infiltrates, lung edema and respiratory failure. Here, we examined the efficacy the DNA methyl transferase (DNMT) inhibitor 5-Aza 2-deoxycytidine (Aza), the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA), as well as the combination therapy of Aza and TSA (Aza+TSA) provides in the protection of ALI. In LPS-induced mouse ALI, post-treatment with a single dose of Aza+TSA showed substantial attenuation of adverse lung histopathological changes and inflammation. Importantly, these protective effects were due to substantial macrophage phenotypic changes observed in LPS-stimulated macrophages treated with Aza+TSA as compared with untreated LPS-induced macrophages or LPS-stimulated macrophages treated with either drug alone. Further, we observed significantly lower levels of pro-inflammatory molecules and higher levels of anti-inflammatory molecules in LPS-induced macrophages treated with Aza+TSA than in LPS-induced macrophages treated with either drug alone. The protection was ascribed to dual effects by an inhibition of MAPK-HuR-TNF and activation of STAT3-Bcl2 pathways. Combinatorial treatment with Aza+TSA reduces inflammation and promotes an anti-inflammatory M2 macrophage phenotype in ALI, and has a therapeutic potential for patients with sepsis.Â© 2015. Published by The Company of Biologists Ltd.
Use of contact force sensing technology during radiofrequency ablation reduces recurrence of atrial fibrillation: A systematic review and meta-analysis. - Heart rhythm : the official journal of the Heart Rhythm Society
The suboptimal outcomes of atrial fibrillation (AF) ablation have been attributed to lack of transmural lesions during pulmonary vein isolation. The advent of contact force (CF) sensing technology enables real-time assessment of the applied force at the catheter-tissue interface and increases the chances of transmural lesions. We sought to perform a meta-analysis of data from eligible studies to delineate the true impact of CF technology. Database searches through April 2015 identified 9 eligible studies (enrolling 1148 patients). The relative risk of AF recurrence at follow-up was used as the primary end point and assessed with random-effects meta-analysis. Radiofrequency (RF) duration, total procedure length, and fluoroscopy exposure were assessed as secondary outcomes using weighted mean difference with the random-effects model. Compared with standard technology, the use of CF technology showed a 37% reduction (relative risk 0.63; 95% confidence interval 0.44-0.91; P = .01) in AF recurrence at a median follow-up of 12 months and a 7.3-minute reduction (95% confidence interval -14.05 to -0.55; P = .03) in RF use during ablation. There was no significant difference in total procedure length and fluoroscopy exposure between the 2 groups. In conclusion, this meta-analysis shows that the use of CF technology decreases AF recurrence at a median follow-up of 12 months and also led to decreased use of RF during ablation. There was no difference in total procedure length and fluoroscopy exposure.Copyright Â© 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
Human Induced Pluripotent Stem Cell-Derived Microvesicles Transmit RNAs and Proteins to Recipient Mature Heart Cells Modulating Cell Fate and Behavior. - Stem cells (Dayton, Ohio)
Microvesicles (MVs) are membrane-enclosed cytoplasmic fragments released by normal and activated cells that have been described as important mediators of cell-to-cell communication. Although the ability of human induced pluripotent stem cells (hiPSCs) to participate in tissue repair is being increasingly recognized, the use of hiPSC-derived MVs (hiPSC-MVs) in this regard remains unknown. Accordingly, we investigated the ability of hiPSC-MVs to transfer bioactive molecules including mRNA, microRNA (miRNA), and proteins to mature target cells such as cardiac mesenchymal stromal cells (cMSCs), and we next analyzed effects of hiPSC-MVs on fate and behavior of such target cells. The results show that hiPSC-MVs derived from integration-free hiPSCs cultured under serum-free and feeder-free conditions are rich in mRNA, miRNA, and proteins originated from parent cells; however, the levels of expression vary between donor cells and MVs. Importantly, we found that transfer of hiPSC components by hiPSC-MVs impacted on transcriptome and proteomic profiles of target cells as well as exerted proliferative and protective effects on cMSCs, and enhanced their cardiac and endothelial differentiation potential. hiPSC-MVs also transferred exogenous transcripts from genetically modified hiPSCs that opens new perspectives for future strategies to enhance MV content. We conclude that hiPSC-MVs are effective vehicles for transferring iPSC attributes to adult somatic cells, and hiPSC-MV-mediated horizontal transfer of RNAs and proteins to injured tissues may be used for therapeutic tissue repair. In this study, for the first time, we propose a new concept of use of hiPSCs as a source of safe acellular bioactive derivatives for tissue regeneration.Â© AlphaMed Press.
Effects of Intracoronary Infusion of Escalating Doses of Cardiac Stem Cells in Rats With Acute Myocardial Infarction. - Circulation. Heart failure
Although c-kit(pos) cardiac stem cells (CSCs) preserve left ventricular (LV) function and structure after myocardial infarction, CSC doses have been chosen arbitrarily, and the dose-effect relationship is unknown.Rats underwent a 90-minute coronary occlusion followed by 35 days of reperfusion. Vehicle or CSCs at 5 escalating doses (0.3Ã—10(6), 0.75Ã—10(6), 1.5Ã—10(6), 3.0Ã—10(6), and 6.0Ã—10(6) cells/heart) were given intracoronarily 4 h after reperfusion. The lowest dose (0.3Ã—10(6)) had no effect on LV function and morphology, whereas 0.75, 1.5, and 3.0Ã—10(6) significantly improved regional and global LV function (echocardiography and hemodynamic studies). These 3 doses had similar effects on echocardiographic parameters (infarct wall thickening fraction, LV end-systolic and end-diastolic volumes, LV ejection fraction) and hemodynamic variables (LV end-diastolic pressure, LV dP/dtmax, preload adjusted maximal power, end-systolic elastance, preload recruitable stroke work) and produced similar reductions in apoptosis, scar size, infarct wall thinning, and LV expansion index and similar increases in viable myocardium in the risk region (morphometry). Infusion of 6.0Ã—10(6) CSCs markedly increased postprocedural mortality. Green fluorescent protein and 5-bromo-2'-deoxyuridine staining indicated that persistence of donor cells and formation of new myocytes were negligible with all doses.Surprisingly, in this rat model of acute myocardial infarction, the dose-response relationship for intracoronary CSCs is flat. A minimal dose between 0.3 and 0.75Ã—10(6) is necessary for efficacy; above this threshold, a 4-fold increase in cell number does not produce greater improvement in LV function or structure. Further increases in cell dose are harmful.Â© 2015 American Heart Association, Inc.
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