Patient selection.

<p>Flow-chart detailing patient selection. ce-CMR: contrast-enhanced Cardiac Magnetic Resonance; FU: follow-up.</p

Role of Circulating Angiotensin Converting Enzyme 2 in Left Ventricular Remodeling following Myocardial Infarction: A Prospective Controlled Study

<div><p>Angiotensin-converting enzyme 2 (ACE2) cleaves Angiotensin-II to Angiotensin-(1–7), a cardioprotective peptide. Serum soluble ACE2 (sACE2) activity is raised in chronic heart failure, suggesting a compensatory role in left ventricular dysfunction<b>.</b> Our aim was to study the relationship between sACE2 activity, infarct size, left ventricular systolic function and remodeling following ST-elevation myocardial infarction (STEMI). A contrast-enhanced cardiac magnetic resonance study was performed acutely in 95 patients with first STEMI and repeated at 6 months to measure LV end-diastolic volume index, ejection fraction and infarct size. Baseline sACE2 activities, measured by fluorescent enzymatic assay 24 to 48 hours and at 7 days from admission, were compared to that obtained in 22 matched controls. Patients showed higher sACE2 at baseline than controls (104.4 [87.4–134.8] vs 74.9 [62.8–87.5] RFU/µl/hr, p<0.001). At seven days, sACE2 activity significantly increased from baseline (115.5 [92.9–168.6] RFU/µl/hr, p<0.01). An inverse correlation between sACE2 activity with acute and follow-up ejection fraction was observed (r = −0.519, p<0.001; r = −0.453, p = 0.001, respectively). Additionally, sACE2 directly correlated with infarct size (r = 0.373, p<0.001). Both, infarct size (β = −0.470 [95%CI:−0.691:−0.248], p<0.001) and sACE2 at 7 days (β = −0.025 [95%CI:−0.048:−0.002], p = 0.030) were independent predictors of follow-up ejection fraction. Patients with sACE2 in the upper tertile had a 4.4 fold increase in the incidence of adverse left ventricular remodeling (95% confidence interval: 1.3 to 15.2, p = 0.027). In conclusion, serum sACE2 activity rises in relation to infarct size, left ventricular systolic dysfunction and is associated with the occurrence of left ventricular remodeling.</p></div

Serum levels of Growth Arrest-Specific 6 protein and soluble AXL in patients with ST-segment elevation myocardial infarction

Background: Serum soluble AXL (sAXL) and its ligand, Growth Arrest-Specific 6 protein (GAS6), intervene in tissue repair processes. AXL is increased in end-stage heart failure, but the role of GAS6 and sAXL in ST-segment elevation myocardial infarction (STEMI) is unknown. Objectives: To study the association of sAXL and GAS6 acutely and six months following STEMI with heart failure and left ventricular remodelling. Methods: GAS6 and sAXL were measured by enzyme-linked immunosorbent assay at one day, seven days and six months in 227 STEMI patients and 20 controls. Contrast-enhanced magnetic resonance was performed during admission and at six months to measure infarct size and left ventricular function. Results: GAS6, but not sAXL, levels during admission were significantly lower in STEMI than in controls. AXL increased progressively over time (p1) had higher values of sAXL at day 1 (48.9±11.9 vs. 44.0±10.7 ng/ml; p<0.05) and at six months (63.3±15.4 vs. 55.9±13.7 ng/ml; p<0.05). GAS6 levels were not different among subjects with heart failure or left ventricular remodelling. By multivariate analysis including infarct size, Killip class and sAXL at seven days, only the last two were independent predictors of left ventricular remodelling (odds ratio 2.24 (95% confidence interval: 1.08-4.63) and odds ratio 1.04 (95% confidence interval: 1.00-1.08) respectively). Conclusion: sAXL levels increased following STEMI. Patients with heart failure and left ventricular remodelling have higher sAXL levels acutely and at six month follow-up. These findings suggest a potential role of the GAS6-AXL system in the pathophysiology of left ventricular remodelling following STEMI

Correlation between sACE2 activity and infarct size.

<p>A weak but significant correlation was observed between infarct size and sACE2 activity at 7 days (panel A) and at 6 months follow-up (panel B). FU: Follow-up. sACE2: Serum Angiotensin Converting Enzyme 2; LV: left ventricular; RFU: relative fluorometric units.</p

sACE2 activity and LV systolic function.

<p>Scatter-plots showing a statistically significant correlation between ACE2 activity at 7 days and EF during admission (panel A) and at 6 months follow-up (panel B). sACE2: Serum Angiotensin Converting Enzyme 2; EF: ejection fraction; RFU: relative fluorometric units.</p

sACE2 laboratory results.

<p>Data expressed as relative fluorometric units per microliter per hour (RFU/µl/hr).</p>*<p>p<0.001 for comparison between baseline values in controls and STEMI patients by Mann-Whitney U test.</p>**<p>p<0.01 for comparison between baseline and 7 days values in patients by paired Wilcoxon test.</p><p>sACE2: Serum Angiotensin Converting Enzyme 2.</p

Population demographic characteristics.

<p>Data expressed as mean (SD) or number (%).</p

Relación entre el volumen extracelular en el miocardio remoto y el remodelado ventricular en el síndrome coronario agudo con elevación del segmento st

Trabajo presentado en el SEC 2018: Congreso de las Enfermedades Cardiovasculares, celebrado en Sevilla, del 25 al 27 de octubre de 2018Previamente hemos demostrado un aumento progresivo de AXL circulante (sAXL) post-IAMCEST, un receptor transmembrana relacionado con la regulación inflamatoria. Niveles más altos se asocian a insuficiencia cardiaca y son un predictor independiente de remodelado ventricular adverso. Métodos: Para determinar si la contribución de sAXL en el remodelado se produce por un aumento de la fibrosis en el miocardio remoto, se determinó el volumen extracelular (VEC) mediante resonancia cardiaca en la fase aguda y a los 6 meses post-IAMCEST en una población de 33 individuos. Se determinaron los niveles de sAXL a las 24h, 7 días y 6 meses mediante ELISA. Resultados: Los valores de VEC en el miocardio remoto se incrementaron en la mayoría de pacientes a los 6 meses del infarto (23,92 ± 2,99% basal frente a 25,59 ± 2,67% a los 6 meses, p 28,5% en el seguimiento tenían mayores niveles de sAXL en el primer día (53,6 ± 17,9 ng/ml frente a 39,9 ± 14,1 ng/ml; p 0,029). VEC basal VEC seguimiento r p r p iVTDVI inicial 0,361 0,028 0,288 0,043 iVTSVI inicial 0,280 0,093 0,311 0,028 iVTDVI 6m 0,213 0,226 0,356 0,010 iVTSVI 6m 0,265 0,130 0,368 0,008 BNP admisión 0,323 0,051 0,317 0,023 Conclusiones: sAXL ejerce su modulación sobre el remodelado adverso posinfarto a través del aumento de la fibrosis en el miocardio remoto, de manera independiente a otros mediadores neurohormonales como en BNP.Peer reviewe