Prediction of Reverse Remodeling at Cardiac MR Imaging Soon after First ST-Segment-Elevation Myocardial Infarction: Results of a Large Prospective Registry

[EN] Conclusion: Assessment of infarct size and MVO with cardiac MR imaging soon after STEMI enables one to make a decision in the prediction of reverse remodeling. (C) RSNA, 2015Supported by the Instituto de Salud Carlos III and FEDER (grant PI1400271) and the Generalitat Valenciana (grant PROMETEO/2013/007).Bodi, V.; Monmeneu, J.; Ortiz-Perez, J.; López-Lereu, M.; Bonanad, C.; Husser, O.; Minana, G.... (2016). Prediction of Reverse Remodeling at Cardiac MR Imaging Soon after First ST-Segment-Elevation Myocardial Infarction: Results of a Large Prospective Registry. Radiology. 278(1):54-63. https://doi.org/10.1148/radiol.2015142674S5463278

Perpendicular magnetic anisotropy in granular multilayers of COPD alloyed nanoparticles

Co-Pd multilayers obtained by Pd capping of pre-deposited Co nanoparticles on amorphous alumina are systematically studied by means of high-resolution transmission electron microscopy, x-ray diffraction, extended x-ray absorption fine structure, SQUID-based magnetometry, and x-ray magnetic circular dichroism. The films are formed by COPD alloyed nanoparticles self-organized across the layers, with the interspace between the nanoparticles filled by the non-alloyed Pd metal. The nanoparticles show atomic arrangements compatible with short-range chemical order of L10 strucure type. The collective magnetic behavior is that of ferromagnetically coupled particles with perpendicular magnetic anisotropy, irrespective of the amount of deposited Pd. For increasing temperature three magnetic phases are identified: hard ferromagnetic with strong coercive field, soft-ferromagnetic as in an amorphous asperomagnet, and superparamagnetic. Increasing the amount of Pd in the system leads to both magnetic hardness increment and higher transition temperatures. Magnetic total moments of 1.77(4) µB and 0.45(4) µB are found at Co and Pd sites, respectively, where the orbital moment of Co, 0.40(2) µB, is high, while that of Pd is negligible. The effective magnetic anisotropy is the largest in the capping metal series (Pd, Pt, W, Cu, Ag, Au), which is attributed to the interparticle interaction between de nanoparticles, in addition to the intraparticle anisotropy arising from hybridization between the 3d-4d bands associated to the Co and Pd chemical arrangement in a L10 structure type

Incidence, Outcomes, and Predictors of Ventricular Thrombus after Reperfused ST-Segment-Elevation Myocardial Infarction by Using Sequential Cardiac MR Imaging

[EN] Purpose: To characterize the incidence, outcomes, and predictors of left ventricular (LV) thrombus by using sequential cardiac magnetic resonance (MR) imaging after ST-segment-elevation myocardial infarction (STEMI). Materials and Methods: Written informed consent was obtained from all patients, and the study protocol was approved by the committee on human research. In a cohort of 772 patients with STEMI, 392 (mean age, 58 years; range, 24-89 years) were retrospectively selected who were studied with cardiac MR imaging at 1 week and 6 months. Cardiac MR imaging guided the initiation and withdrawal of anticoagulants. Patients with LV thrombus at 6 months were restudied at 1 year. For predicting the occurrence of LV thrombus, a multiple regression model was applied. Results: LV thrombus was detected in 27 of 392 patients (7%): 18 (5%) at 1 week and nine (2%) at 6 months. LV thrombus resolved in 22 of 25 patients (88%) restudied within the first year. During a mean follow-up of 181 weeks 6 168, patients with LV thrombus displayed a very low rate of stroke (0%), peripheral embolism (0%), and severe hemorrhage (n = 1, 3.7%). LV ejection fraction (LVEF) less than 50% (P < .001) and anterior infarction (P = .008) independently helped predict LV thrombus. The incidence of LV thrombus was as follows: (a) nonanterior infarction, LVEF 50% or greater (one of 135, 1%); (b) nonanterior infarction, LVEF less than 50% (one of 50, 2%); (c) anterior infarction, LVEF 50% or greater (two of 92, 2%); and (d) anterior infarction, LVEF less than 50% (23 of 115, 20%) (P < .001 for the trend). Conclusion: Cardiac MR imaging contributes information for the diagnosis and therapy of LV thrombus after STEMI. Patients with simultaneous anterior infarction and LVEF less than 50% are at highest risk. (C) RSNA, 2017Study supported by Instituto de Salud Carlos III and FEDER (CB16/11/00486, PI14/00271, PIE15/00013) and Generalitat Valenciana (PROMETEO/2013/007).Cambronero-Cortinas, E.; Bonanad, C.; Monmeneu, J.; López-Lereu, M.; Gavara-Doñate, J.; De Dios, E.; Rios, C.... (2017). Incidence, Outcomes, and Predictors of Ventricular Thrombus after Reperfused ST-Segment-Elevation Myocardial Infarction by Using Sequential Cardiac MR Imaging. Radiology. 284(2):372-380. https://doi.org/10.1148/radiol.2017161898S372380284

Effect of chronic exercise on myocardial electrophysiological heterogeneity and stability. Role of intrinsic cholinergic neurons: A study in the isolated rabbit heart

[EN] A study has been made of the effect of chronic exercise on myocardial electrophysiological heterogeneity and stability, as well as of the role of cholinergic neurons in these changes. Determinations in hearts from untrained and trained rabbits on a treadmill were performed. The hearts were isolated and perfused. A pacing electrode and a recording multielectrode were located in the left ventricle. The parameters determined during induced VF, before and after atropine (1 mu M), were: fibrillatory cycle length (VV), ventricular functional refractory period (FRPVF), normalized energy (NE) of the fibrillatory signal and its coefficient of variation (CV), and electrical ventricular activation complexity, as an approach to myocardial heterogeneity and stability. The VV interval was longer in the trained group than in the control group both prior to atropine (78 +/- 10 vs. 68 +/- 10 ms) and after atropine (76 +/- 8 vs. 67 +/- 10 ms). Likewise, FRPVF was longer in the trained group than in the control group both prior to and after atropine (53 +/- 8 vs. 42 +/- 7 ms and 50 +/- 6 vs. 40 +/- 6 ms, respectively), and atropine did not modify FRPVF. The CV of FRPVF was lower in the trained group than in the control group prior to atropine (12.5 +/- 1.5% vs. 15.1 +/- 3.8%) and, decreased after atropine (15.1 +/- 3.8% vs. 12.2 +/- 2.4%) in the control group. The trained group showed higher NE values before (0.40 +/- 0.04 vs. 0.36 +/- 0.05) and after atropine (0.37 +/- 0.04 vs. 0.34 +/- 0.06; p = 0.08). Training decreased the CV of NE both before (23.3 +/- 2% vs. 25.2 +/- 4%; p = 0.08) and after parasympathetic blockade (22.6 +/- 1% vs. 26.1 +/- 5%). Cholinergic blockade did not modify these parameters within the control and trained groups. Activation complexity was lower in the trained than in the control animals before atropine (34 +/- 8 vs. 41 +/- 5), and increased after atropine in the control group (41 +/- 5 vs. 48 +/- 9, respectively). Thus, training decreases the intrinsic heterogeneity of the myocardium, increases electrophysiological stability, and prevents some modifications due to muscarinic block.This research was supported by the Spanish Ministry of Education and Science, (DEP2007-73234-C03-01 to AMA), http://www.mecd.gob.es/portada-mecd/; and the Generalitat Valenciana (PROMETEO 2010/093 to FJC, and FPI/2008/003 to MZ), http://www.gva.es/va/inicio/presentacion; jsessionid=ydprbDQZTsCTz85W1Such-Miquel, L.; Brines-Ferrando, L.; Alberola, A.; Zarzoso Muñoz, M.; Chorro Gasco, FJ.; Guerrero-Martínez, JF.; Parra-Giraldo, G.... (2018). Effect of chronic exercise on myocardial electrophysiological heterogeneity and stability. Role of intrinsic cholinergic neurons: A study in the isolated rabbit heart. PLoS ONE. 13(12). https://doi.org/10.1371/journal.pone.0209085S1312Billman, G. E. (2002). Aerobic exercise conditioning: a nonpharmacological antiarrhythmic intervention. Journal of Applied Physiology, 92(2), 446-454. doi:10.1152/japplphysiol.00874.2001Billman, G. E. (2006). A comprehensive review and analysis of 25 years of data from an in vivo canine model of sudden cardiac death: Implications for future anti-arrhythmic drug development. Pharmacology & Therapeutics, 111(3), 808-835. doi:10.1016/j.pharmthera.2006.01.002Dor-Haim, H., Berenfeld, O., Horowitz, M., Lotan, C., & Swissa, M. (2013). Reduced Ventricular Arrhythmogeneity and Increased Electrical Complexity in Normal Exercised Rats. PLoS ONE, 8(6), e66658. doi:10.1371/journal.pone.0066658Hamer, M., & Stamatakis, E. (2008). Physical Activity and Cardiovascular Disease: Directions for Future Research. The Open Sports Sciences Journal, 1(1), 1-2. doi:10.2174/1875399x00801010001Powers, S. K., Smuder, A. J., Kavazis, A. N., & Quindry, J. C. (2014). Mechanisms of Exercise-Induced Cardioprotection. Physiology, 29(1), 27-38. doi:10.1152/physiol.00030.2013Hull, S. S., Vanoli, E., Adamson, P. B., Verrier, R. L., Foreman, R. D., & Schwartz, P. J. (1994). Exercise training confers anticipatory protection from sudden death during acute myocardial ischemia. Circulation, 89(2), 548-552. doi:10.1161/01.cir.89.2.548Hajnal, Á., Nagy, O., Litvai, Á., Papp, J., Parratt, J. R., & Végh, Á. (2005). Nitric oxide involvement in the delayed antiarrhythmic effect of treadmill exercise in dogs. Life Sciences, 77(16), 1960-1971. doi:10.1016/j.lfs.2005.02.015Such, L., Alberola, A. M., Such-Miquel, L., López, L., Trapero, I., Pelechano, F., … Chorro, F. J. (2008). Effects of chronic exercise on myocardial refractoriness: a study on isolated rabbit heart. Acta Physiologica, 193(4), 331-339. doi:10.1111/j.1748-1716.2008.01851.xZarzoso, M., Such-Miquel, L., Parra, G., Brines-Ferrando, L., Such, L., Chorro, F. J., … Alberola, A. (2011). The training-induced changes on automatism, conduction and myocardial refractoriness are not mediated by parasympathetic postganglionic neurons activity. European Journal of Applied Physiology, 112(6), 2185-2193. doi:10.1007/s00421-011-2189-4Billman, G. E. (2009). Cardiac autonomic neural remodeling and susceptibility to sudden cardiac death: effect of endurance exercise training. American Journal of Physiology-Heart and Circulatory Physiology, 297(4), H1171-H1193. doi:10.1152/ajpheart.00534.2009HAN, J., & MOE, G. K. (1964). Nonuniform Recovery of Excitability in Ventricular Muscle. Circulation Research, 14(1), 44-60. doi:10.1161/01.res.14.1.44Beaumont, E., Salavatian, S., Southerland, E. M., Vinet, A., Jacquemet, V., Armour, J. A., & Ardell, J. L. (2013). Network interactions within the canine intrinsic cardiac nervous system: implications for reflex control of regional cardiac function. The Journal of Physiology, 591(18), 4515-4533. doi:10.1113/jphysiol.2013.259382Armour, J. A. (2008). Potential clinical relevance of the ‘little brain’ on the mammalian heart. Experimental Physiology, 93(2), 165-176. doi:10.1113/expphysiol.2007.041178Abramochkin, D. V., Nurullin, L. F., Borodinova, A. A., Tarasova, N. V., Sukhova, G. S., Nikolsky, E. E., & Rosenshtraukh, L. V. (2009). Non-quantal release of acetylcholine from parasympathetic nerve terminals in the right atrium of rats. Experimental Physiology, 95(2), 265-273. doi:10.1113/expphysiol.2009.050302CHORRO, F. J., CANOVES, J., GUERRERO, J., MAINAR, L., SANCHIS, J., SORIA, E., … LOPEZ-MERINO, V. (2000). Opposite Effects of Myocardial Stretch and Verapamil on the Complexity of the Ventricular Fibrillatory Pattern: An Experimental Study. Pacing and Clinical Electrophysiology, 23(11), 1594-1603. doi:10.1046/j.1460-9592.2000.01594.xSuch, L., Rodriguez, A., Alberola, A., Lopez, L., Ruiz, R., Artal, L., … Chorro, F. J. (2002). Intrinsic changes on automatism, conduction, and refractoriness by exercise in isolated rabbit heart. Journal of Applied Physiology, 92(1), 225-229. doi:10.1152/jappl.2002.92.1.225Duytschaever, M., Mast, F., Killian, M., Blaauw, Y., Wijffels, M., & Allessie, M. (2001). Methods for Determining the Refractory Period and Excitable Gap During Persistent Atrial Fibrillation in the Goat. Circulation, 104(8), 957-962. doi:10.1161/hc3401.093156Wijffels, M. C. E. F., Kirchhof, C. J. H. J., Dorland, R., & Allessie, M. A. (1995). Atrial Fibrillation Begets Atrial Fibrillation. Circulation, 92(7), 1954-1968. doi:10.1161/01.cir.92.7.1954Zaitsev, A. V., Berenfeld, O., Mironov, S. F., Jalife, J., & Pertsov, A. M. (2000). Distribution of Excitation Frequencies on the Epicardial and Endocardial Surfaces of Fibrillating Ventricular Wall of the Sheep Heart. Circulation Research, 86(4), 408-417. doi:10.1161/01.res.86.4.408Armour, J. A., Collier, K., Kember, G., & Ardell, J. L. (1998). Differential selectivity of cardiac neurons in separate intrathoracic autonomic ganglia. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 274(4), R939-R949. doi:10.1152/ajpregu.1998.274.4.r939Armour, J. A., & Hopkins, D. A. (1990). Activity of in vivo canine ventricular neurons. American Journal of Physiology-Heart and Circulatory Physiology, 258(2), H326-H336. doi:10.1152/ajpheart.1990.258.2.h326D’Souza, A., Bucchi, A., Johnsen, A. B., Logantha, S. J. R. J., Monfredi, O., Yanni, J., … Boyett, M. R. (2014). Exercise training reduces resting heart rate via downregulation of the funny channel HCN4. Nature Communications, 5(1). doi:10.1038/ncomms4775Sartiani, L., Romanelli, M., Mugelli, A., & Cerbai, E. (2015). Updates on HCN Channels in the Heart: Function, Dysfunction and Pharmacology. Current Drug Targets, 16(8), 868-876. doi:10.2174/1389450116666150531152047Herrmann, S., Layh, B., & Ludwig, A. (2011). Novel insights into the distribution of cardiac HCN channels: An expression study in the mouse heart. Journal of Molecular and Cellular Cardiology, 51(6), 997-1006. doi:10.1016/j.yjmcc.2011.09.005Welch, P. (1967). The use of fast Fourier transform for the estimation of power spectra: A method based on time averaging over short, modified periodograms. IEEE Transactions on Audio and Electroacoustics, 15(2), 70-73. doi:10.1109/tau.1967.116190

The monocyte-macrophage axis in the intestine

Macrophages are one of the most abundant leucocytes in the intestinal mucosa where they are essential for maintaining homeostasis. However, they are also implicated in the pathogenesis of disorders such as inflammatory bowel disease (IBD), offering potential targets for novel therapies. Here we discuss the function of intestinal monocytes and macrophages during homeostasis and describe how these populations and their functions change during infection and inflammation. Furthermore, we review the current evidence that the intestinal macrophage pool requires continual renewal from circulating blood monocytes, unlike most other tissue macrophages which appear to derive from primitive precursors that subsequently self-renew

Magnetic resonance microscopy and correlative histopathology of the infarcted heart

Altres ajuts:The present study was supported by the EU Joint Programming Initiative 'A Healthy Diet for a Healthy Life' (JPI HDHL INTIMIC-085), Generalitat Valenciana (GV/2018/116), INCLIVA and Universitat de Valencia (program VLC-BIOCLINIC 20-nanomIRM-2016A).Delayed enhancement cardiovascular magnetic resonance (MR) is the gold-standard for non-invasive assessment after myocardial infarction (MI). MR microscopy (MRM) provides a level of detail comparable to the macro objective of light microscopy. We used MRM and correlative histopathology to identify infarct and remote tissue in contrast agent-free multi-sequence MRM in swine MI hearts. One control group (n = 3 swine) and two experimental MI groups were formed: 90 min of ischemia followed by 1 week (acute MI = 6 swine) or 1 month (chronic MI = 5 swine) reperfusion. Representative samples of each heart were analysed by contrast agent-free multi-sequence (T1-weighting, T2-weighting, T2*-weighting, T2-mapping, and T2*-mapping). MRM was performed in a 14-Tesla vertical axis imager (Bruker-AVANCE 600 system). Images from MRM and the corresponding histopathological stained samples revealed differences in signal intensities between infarct and remote areas in both MI groups (p-value < 0.001). The multivariable models allowed us to precisely classify regions of interest (acute MI: specificity 92% and sensitivity 80%; chronic MI: specificity 100% and sensitivity 98%). Probabilistic maps based on MRM images clearly delineated the infarcted regions. As a proof of concept, these results illustrate the potential of MRM with correlative histopathology as a platform for exploring novel contrast agent-free MR biomarkers after MI

Differential mortality association of loop diuretic dosage according to blood urea nitrogen and carbohydrate antigen 125 following a hospitalization for acute heart failure

AimsRecent observations in chronic stable heart failure suggest that high-dose loop diuretics (HDLDs) have detrimental prognostic effects in patients with high blood urea nitrogen (BUN), but recent findings have also indicated that diuretics may improve renal function. Carbohydrate antigen 125 (CA125) has been shown to be a surrogate of systemic congestion. We sought to explore whether BUN and CA125 modulate the mortality risk associated with HDLDs following a hospitalization for acute heart failure (AHF).Methods and resultsWe analysed 1389 consecutive patients discharged for AHF. CA125 and BUN were measured at a mean of 72 ± 12 h after admission. HDLDs (≥120 mg/day in furosemide equivalent dose) were interacted to a four-level variable according to CA125 (>35 U/mL) and BUN (above the median), and related to all-cause mortality. At a median follow-up of 21 months, 561 (40.4%) patients died. The use of HDLDs was independently associated with increased mortality [hazard ratio (HR) 1.23, 95% confidence interval (CI) 1.01–1.50], but this association was not homogeneous across CA125–BUN categories (P for interaction <0.001). In patients with normal CA125, use of HDLDs was associated with high mortality if BUN was above the median (HR 2.29, 95% 1.51–3.46), but not in those with BUN below the median (HR 1.22, 95% CI 0.73–2.04). Conversely, in patients with high CA125, HDLDs showed an association with increased survival if BUN was above the median (HR 0.73, 95% CI 0.55–0.98) but was associated with increased mortality in those with BUN below the median (HR 1.94, 95% CI 1.36–2.76).ConclusionThe risk associated with HDLDs in patients after hospitalization for AHF was dependent on the levels of BUN and CA125. The information provided by these two biomarkers may be helpful in tailoring the dose of loop diuretics at discharge for AHF

Tissue Microenvironments Define and Get Reinforced by Macrophage Phenotypes in Homeostasis or during Inflammation, Repair and Fibrosis

Current macrophage phenotype classifications are based on distinct in vitro culture conditions that do not adequately mirror complex tissue environments. In vivo monocyte progenitors populate all tissues for immune surveillance which supports the maintenance of homeostasis as well as regaining homeostasis after injury. Here we propose to classify macrophage phenotypes according to prototypical tissue environments, e.g. as they occur during homeostasis as well as during the different phases of (dermal) wound healing. In tissue necrosis and/or infection, damage- and/or pathogen-associated molecular patterns induce proinflammatory macrophages by Toll-like receptors or inflammasomes. Such classically activated macrophages contribute to further tissue inflammation and damage. Apoptotic cells and antiinflammatory cytokines dominate in postinflammatory tissues which induce macrophages to produce more antiinflammatory mediators. Similarly, tumor-associated macrophages also confer immunosuppression in tumor stroma. Insufficient parenchymal healing despite abundant growth factors pushes macrophages to gain a profibrotic phenotype and promote fibrocyte recruitment which both enforce tissue scarring. Ischemic scars are largely devoid of cytokines and growth factors so that fibrolytic macrophages that predominantly secrete proteases digest the excess extracellular matrix. Together, macrophages stabilize their surrounding tissue microenvironments by adapting different phenotypes as feed-forward mechanisms to maintain tissue homeostasis or regain it following injury. Furthermore, macrophage heterogeneity in healthy or injured tissues mirrors spatial and temporal differences in microenvironments during the various stages of tissue injury and repair. Copyright (C) 2012 S. Karger AG, Base

P and R Wave Detection in Complete Congenital Atrioventricular Block

Complete atrioventricular block (type III AVB) is characterized by an absence of P wave transmission to ventricles. This implies that QRS complexes are generated in an autonomous way and are not coordinated with P waves. This work introduces a new algorithm for the detection of P waves for this type of pathology using non-invasive electrocardiographic surface leads. The proposed algorithm is divided into three stages. In the first stage, the R waves located by a QRS detector are used to generate the RR series and time references for the other stages of the algorithm. In the second stage, the ventricular activity (QT segment) is removed by using an adaptive filter that obtains an averaged pattern of the QT segment. In the third stage, a new P wave detector is applied to the residual signal obtained after QT cancellation in order to detect P wave locations and get the PP time series. Eight Holter records from patients with congenital type III AVB were used to verify the proposed algorithm. Although further improvements should be made to improve the algorithm¿s performance, the results obtained show high average values of sensitivity (90.52 %) and positive prediction (90.98%)

Autoantibodies against the immunodominant sCha epitope discriminate the risk of sudden death in chronic Chagas cardiomyopathy

In Chagas disease (ChD) caused by Trypanosoma cruzi, new biomarkers to predict chronic cardiac pathology are urgently needed. Previous studies in chagasic patients with mild symptomatology showed that antibodies against the immunodominant R3 epitope of sCha, a fragment of the human basic helix-loop-helix transcription factor like 5, correlated with cardiac pathology. To validate sCha as a biomarker and to understand the origin of anti-sCha antibodies, we conducted a multicenter study with several cohorts of chagasic patients with severe cardiac symptomatology. We found that levels of antibodies against sCha discriminated the high risk of sudden death, indicating they could be useful for ChD prognosis. We investigated the origin of the antibodies and performed an alanine scan of the R3 epitope. We identified a minimal epitope MRQLD, and a BLAST search retrieved several T. cruzi antigens. Five of the hits had known or putative functions, of which phosphonopyruvate decarboxylase showed the highest cross-reactivity with sCha, confirming the role of molecular mimicry in the development of anti-sCha antibodies. Altogether, we demonstrate that the development of antibodies against sCha, which originated by molecular mimicry with T. cruzi antigens, could discriminate electrocardiographic alterations associated with a high risk of sudden death.Ministerio de Economía y competitividad and Fondo Europeo de Desarrollo Regional (SAF2015-63868-R (MINECO/FEDER) to N.G., and SAF2016-75988-R (MINECO/FEDER) to M.F.); Ministerio de Ciencia, Innovación y Universidades-Agencia Estatal de Investigación and Fondo Europeo de Desarrollo Regional (PGC2018-096132-BI00 (MICINN/FEDER) to N.G.); Universidad Autónoma de Madrid-Banco de Santander Inter-University Cooperation Grant with Latin América (CEAL-AL/2015-12 to N.G.); Red de Investigación de Centros de Enfermedades Tropicales (RICET RD12/0018/0004 to M.F.); and Comunidad de Madrid (S-2010/BMD-2332 to M.F.). CBMSO institutional grants from Fundación Ramón Areces and Banco de Santande